Infection intensity-dependent accuracy of reagent strip for the diagnosis of Schistosoma haematobium and estimation of treatment prevalence thresholds.

BACKGROUND: Reagent strip to detect microhematuria as a proxy for Schistosoma haematobium infections has been considered an alternative to urine filtration for individual diagnosis and community-based estimates of treatment needs for preventive chemotherapy. However, the diagnostic accuracy of reagent strip needs further investigation, particularly at low infection intensity levels. METHODS: We used existing data from a study conducted in Tanzania that employed urine filtration and reagent strip testing for S. haematobium in two villages, including a baseline and six follow-up surveys after praziquantel treatment representing a wide range of infection prevalence. We developed a Bayesian model linking individual S. haematobium egg count data based on urine filtration to reagent strip binary test results available on multiple days and estimated the relation between infection intensity and sensitivity of reagent strip. Furthermore, we simulated data from 3,000 hypothetical populations with varying mean infection intensity to infer on the relation between prevalence observed by urine filtration and the interpretation of reagent strip readings. PRINCIPAL FINDINGS: Reagent strip showed excellent sensitivity even for single measurement reaching 100% at around 15 eggs of S. haematobium per 10 ml of urine when traces on reagent strip were considered positive. The corresponding specificity was 97%. When traces were considered negative, the diagnostic accuracy of the reagent strip was equivalent to urine filtration data obtained on a single day. A 10% and 50% urine filtration prevalence based on a single day sampling corresponds to 11.2% and 48.6% prevalence by reagent strip, respectively, when traces were considered negative, and 17.6% and 57.7%, respectively, when traces were considered positive. CONCLUSIONS/SIGNIFICANCE: Trace results should be included in reagent strip readings when high sensitivity is required, but excluded when high specificity is needed. The observed prevalence of reagent strip results, when traces are considered negative, is a good proxy for prevalence estimates of S. haematobium infection by urine filtration on a single day.

Comparison of Two Different Semiquantitative Urinary Dipstick Tests with Albumin-to-Creatinine Ratio for Screening and Classification of Albuminuria According to KDIGO. A Diagnostic Test Study.

BACKGROUND: Semiquantitative dipstick tests are utilized for albuminuria screening. METHODS: In a prospective cross-sectional survey, we analyzed the diagnostic test validity of the semiquantitative colorimetric indicator-dye-based Combur9-Test® and the albumin-specific immunochromatographic assay Micral-Test® for the detection of albuminuria, the distribution of the semiquantitative measurements within the albuminuria stages according to KDIGO, and the utility for albuminuria screening compared with an albumin-to-creatinine ratio (ACR) in a walk-in population. RESULTS: In 970 subjects, albuminuria (≥30 mg/g) was detected in 12.7% (95% CI 85.6-96.3%) with the ACR. Sensitivity was 82.9% (95% CI 75.1-89.1%) and 91.9% (95% CI 88.7-96.9%) and specificity 71.5% (95% CI 68.4-74.6%) and 17.5% (95% CI 15.0-20.2%) for the Combur9-Test® and Micral-Test®, respectively. Correct classification to KDIGO albuminuria stages A2/A3 with the Combur9-Test® was 15.4%, 51.4%, and 87.9% at cut-offs of 30, 100, and ≥300 mg/dL, and with the Micral-Test® it was 1.8%, 10.5%, and 53.6% at cut-offs of 2, 5, and 10 mg/dL, respectively. Overall, disagreement to KDIGO albuminuria was seen in 27% and 73% with the Combur9-Test® and Micral-Test®, respectively. From the total population, 62.5% and 15.3% were correctly ruled out and 2.2% and 1% were missed as false-negatives by the Combur9-Test® and Micral-Test®, respectively. CONCLUSION: Compared to the Combur9-Test®, the utility of the Micral-Test® is limited, because the fraction of correctly ruled out patients is small and a large proportion with a positive Micral-Test® require a subsequent ACR conformation test.

Assessment of diabetes and prediabetes prevalence and predictors by HbA1c in a population from sub-Saharan Africa with a high proportion of anemia: a prospective cross-sectional study.

INTRODUCTION: Epidemiological data about diabetes mellitus (DM) for sub-Saharan Africa (SSA) are scarce and the utility of glycated hemoglobin (HbA1c) to diagnose DM is uncertain in African populations with a high proportion of anemia. RESEARCH DESIGN AND METHODS: In a cross-sectional study, age-adjusted prevalence rates and predictors for DM and pre-DM were prospectively assessed by HbA1c in a semirural walk-in population of Tanzania (n=992). Predictors for DM were calculated by logistic regression. Correlations between HbA1c, hemoglobin, and blood glucose levels were done by Pearson's correlation. RESULTS: Overall, DM and pre-DM prevalence rates were 6.8% (95% CI 5.3 to 8.5) and 25% (95% CI 22.8 to 28.3), respectively. There was an increase in DM prevalence in patients 50-59 (14.9%; 95% CI 9.1 to 22.5), ≥60 years old (18.5%; 95% CI 12.2 to 26.2) and in patients with overweight (9.3%; 95% CI 5.9 to 13.7), obesity (10.9%; 95% CI 6.9 to 16) compared with patients 18-29 years old (2.2%; 95% CI 0.9 to 4.4) (p<0.001) and to normal-weight patients (3.6%; 95% CI 2.1 to 5.6) (p<0.01), respectively. Age (OR 1.08, 95% CI 1.05 to 1.12; p<0.001), body mass index (BMI) (OR 1.10, 95% CI 1.04 to 1.16; p<0.001), and acute infection (OR 3.46, 95% CI 1.02 to 10.8; p=0.038) were predictors for DM. Comparing patients with a BMI of 20 kg/m2 and a BMI of 35 kg/m2, the relative risk for DM increases in average by 2.12-fold (range 1.91-2.24) across the age groups. Comparing patients 20 years old with patients 70 years old, the relative risk for DM increases in average 9.7-fold (range 8.9-10.4) across the BMI groups. Overall, 333 patients (36%) suffered from anemia. Pearson's correlation coefficients (r) between HbA1c and hemoglobin was -0.009 (p=0.779), and between HbA1c and fasting blood glucose and random blood glucose, it was 0.775 and 0.622, respectively (p<0.001). CONCLUSION: We observed a high prevalence of DM and pre-DM, mainly triggered by increasing age and BMI, and provide evidence that HbA1c is suitable to assess DM also in populations of SSA with high proportions of anemia. TRIAL REGISTRATION NUMBER: NCT03458338.

The epidemiology of chronic kidney disease and the association with non-communicable and communicable disorders in a population of sub-Saharan Africa.

In sub-Saharan Africa (SSA), epidemiological data for chronic kidney disease (CKD) are scarce. We conducted a prospective cross-sectional study including 952 patients in an outpatient clinic in Tanzania to explore CKD prevalence estimates and the association with cardiovascular and infectious disorders. According to KDIGO, we measured albumin-to-creatinine ratio and calculated eGFR using CKD-EPI formula. Factors associated with CKD were calculated by logistic regression. Venn diagrams were modelled to visualize interaction between associated factors and CKD. Overall, the estimated CKD prevalence was 13.6% (95% CI 11-16%). Ninety-eight patients (11.2%) (95% CI 9-14%) were categorized as moderate, 12 (1.4%) (95% CI 0-4%) as high, and 9 (1%) (95% CI 0-3%) as very high risk according to KDIGO. History of tuberculosis (OR 3.75, 95% CI 1.66-8.18; p = 0.001) and schistosomiasis (OR 2.49, 95% CI 1.13-5.18; p = 0.02) were associated with CKD. A trend was seen for increasing systolic blood pressure (OR 1.02 per 1 mmHg, 95% CI 1.00-1.03; p = 0.01). Increasing BMI (OR 0.92 per 1kg/m2, 95% CI 0.88-0.96; p = <0.001) and haemoglobin (OR 0.82 per 1g/dL, 95% CI 0.72-0.94; p = 0.004) were associated with risk reduction. Diabetes was associated with albuminuria (OR 2.81, 95% CI 1.26-6.00; p = 0.009). In 85% of all CKD cases at least one of the four most common factors (hypertension, diabetes, anaemia, and history of tuberculosis or schistosomiasis) was associated with CKD. A singular associated factor was found in 61%, two in 14%, and ≥3 in 10% of all CKD cases. We observed a high prevalence estimate for CKD and found that both classical cardiovascular and neglected infectious diseases might be associated with CKD in a semi-rural population of SSA. Our finding provides further evidence for the hypothesis that the "double burden" of non-communicable and endemic infectious diseases might affect kidney health in SSA.

Real-time PCR for detection of Strongyloides stercoralis in human stool samples from Côte d'Ivoire: diagnostic accuracy, inter-laboratory comparison and patterns of hookworm co-infection.

Human infections with the helminth species Strongyloides stercoralis encompass a wide clinical spectrum, ranging from asymptomatic carriage to life-threatening disease. The diagnosis of S. stercoralis is cumbersome and the sensitivity of conventional stool microscopy is low. New molecular tools have been developed to increase sensitivity. We compared the diagnostic accuracy of real-time PCR with microscopy for the detection of S. stercoralis and hookworm in human stool samples, and investigated the inter-laboratory agreement of S. stercoralis-specific real-time PCR in two European laboratories. Stool specimens from 256 randomly selected individuals in rural Côte d'Ivoire were examined using three microscopic techniques (i.e. Kato-Katz, Koga agar plate (KAP) and Baermann (BM)). Additionally, ethanol-fixed stool aliquots were subjected to molecular diagnosis. The prevalence of S. stercoralis and hookworm infection was 21.9% and 52.0%, respectively, whilst co-infections were detected in 35 (13.7%) participants. The diagnostic agreement between real-time PCR and microscopy was excellent when both KAP and BM tested positive for S. stercoralis, but was considerably lower when only one microscopic technique was positive. The sensitivity of KAP, BM and real-time PCR for detection of S. stercoralis as compared to a combination of all diagnostic techniques was 21.4%, 37.5% and 76.8%, respectively. The inter-laboratory agreement of S. stercoralis-specific PCR was substantial (κ=0.63, p<0.001). We conclude that a combination of real-time PCR and stool microscopy shows high accuracy for S. stercoralis diagnosis. Besides high sensitivity, PCR may also enhance specificity by reducing microscopic misdiagnosis of morphologically similar helminth larvae (i.e. hookworm and S. stercoralis) in settings where both helminth species co-exist.

Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study.

BACKGROUND: Shigellae cause severe disease in endemic countries, especially in children. Several efficacy trials have been conducted with candidate vaccines against Shigellae, but the lack of protection, the safety concerns, or manufacturing challenges hindered successful market approval. Conjugated vaccines have been shown to be safe and effective for different pathogens (i.e., Neisseria meningitidis, Shigella pneumonia, Haemophilus influenzae). The bio-conjugation technology, exploited here for the Shigella dysenteriae candidate vaccine, offers a novel and potentially simpler way to develop and produce vaccines against one of the major causes of morbidity and mortality in developing countries. METHODS: A novel S. dysenteriae bioconjugate vaccine (GVXN SD133) made of the polysaccharide component of the Shigella O1 lipopolysaccharide, conjugated to the exotoxin protein A of Pseudomonas aeruginosa (EPA), was evaluated for immunogenicity and safety in healthy adults in a single blind, partially randomized Phase I study. Forty subjects (10 in each dose group; 2 µg or 10 µg with or without aluminium adjuvant) received two injections 60 days apart and were followed-up for 150 days. RESULTS: Both doses and formulations were well tolerated; the safety and reactogenicity profiles were consistent with that of other conjugated vaccines, adjuvanted or not, independent of the dose and the number of injections. The GVXN SD133 vaccine elicited statistically significant O1 specific humoral responses at all time points in all vaccination groups. Between-group comparisons did not show statistically significant differences in geometric mean titers of immunoglobulin G and A at any post-vaccination time point. CONCLUSIONS: This study demonstrated that the GVXN SD133 vaccine has a satisfactory safety profile. It elicited a significant humoral response to Shigella O1 polysaccharides at all doses tested. The protein carrier also elicited functional antibodies, showing the technology's advantages in preserving both sugar and conjugated protein epitopes. This trial is registered at ClinicalTrials.gov (NCT01069471).

Neglected tropical diseases: diagnosis, clinical management, treatment and control.

Branded in 2005, "neglected tropical diseases" have gained traction in terms of advocacy, interest for research, enhanced funding and political will for their control and eventual elimination. Starting with an initial set of 13 neglected tropical diseases--seven helminth, three bacterial and three protozoal infections--the list considerably expanded to more than 40 diseases that now also includes viral, fungal and ectoparasitic infections. In this review, we provide a comprehensive overview of the neglected tropical diseases, their causative agents and the current geographical distribution, including their importance for the general practitioners seeing returning travellers and migrants in Switzerland. We characterise the most important of the neglected tropical diseases in terms of at-risk population, estimated number of infections, annual mortality rates and global burden, including current knowledge gaps. With an emphasis on neglected tropical diseases due to helminths, protozoa and ectoparasites, we review common diagnostic methods and current recommendations for treatment at the population level and the individual patient, thereby juxtaposing the situation in highly endemic countries on one side, with Switzerland on the other. We highlight the clinical presentation and management of the neglected tropical diseases in general and then elaborate on two examples, strongyloidiasis and leptospirosis. Our review provides a global perspective of neglected tropical diseases and we hope that it will prove useful for the general practitioner and clinician in Switzerland and elsewhere to enhance their suspicion index, differential diagnosis, clinical management and treatment, including referral to specialised clinics and laboratories when need be.

Rabies: relevance, prevention, and management in travel medicine.

Rabies is a zoonotic viral disease, transmitted only in mammals. Terrestrial rabies, predominantly transmitted by dogs, is the most important rabies cycle threatening humans. The causative neurotropic virus is a negative-stranded RNA virus of the family Rhabdoviridae, genus Lyssavirus. This genus contains several rabies-related viruses. All variants are known or suspected to cause rabieslike diseases. Transmission occurs by the virus entering through the skin or the mucosa after bites, scratches, or preexisting injuries contaminated by the saliva of an infected mammal. Only 51 human rabies cases that have not been transmitted by animal bites are described.

Acute febrile respiratory reaction after praziquantel treatment during asymptomatic late form of acute schistosomiasis.

Paradoxical reactions (Jarish Herxheimer-like reactions) have been described in patients treated with praziquantel (PZQ) during acute schistosomiasis (infected≤ 3 mo), while PZQ treatment of chronic schistosomiasis is generally considered to be safe. We report an acute febrile reaction with respiratory decompensation following PZQ treatment in a 17-year-old male patient who had no potential (re)exposure to infection for at least 5 months and was therefore considered to have reached the chronic stage of disease. We speculate that the clinical manifestations in our patient constitute a very late paradoxical reaction in an unusually long acute phase of infection.

Travel case scenarios as a demonstration of risk assessment of VFR travelers: introduction to criteria and evidence-based definition and framework.

BACKGROUND: Travel-associated health risks need to be balanced against the positive opportunities associated with interregional travel. As the perceived and real spectrum of health risks related to international travel increase both quantitatively and qualitatively, the need for more discriminating tools in clinical assessment for the purpose of mitigation, public health management, and research are needed. One group of international travelers identified as having increased risk of poor travel-related health outcomes are those who travel with the specific intent of visiting friends or relatives (VFR travelers). Due to variations in defining VFR travel in the health context there are issues in applying this designation uniformly from multiple perspectives. This article supports the standardization of VFR traveler definitions based on objective criteria and provides illustrations of the application of this definition through an illustrated approach to risk assessment based on these criteria and the differentials in the determinants of health between source and destination regions. METHODS: A working group was established by the Migration Health Sub-committee, International Society for Travel Medicine to assess the literature on VFR travel and health, review an evidence-based approach to managing health risk related to travel, and to propose criteria-based definition for VFR travel. The new definition of a VFR is a traveler whose primary purpose of travel is to visit friends or relatives where there is a gradient of epidemiological risk between home and destination. RESULTS: A case scenario discussion of VFR travel defined by criteria and risk assessment based on differential determinants of health is presented in this article. DISCUSSION: The goal of this article is to encourage discussion on travel health evaluation for the most "at risk" populations and to standardize the application of clinical, public health, and research approaches to defining VFR travelers in a risk management context.

The visiting friends or relatives traveler in the 21st century: time for a new definition.

BACKGROUND: Travelers visiting friends or relatives (VFR travelers) are a group identified with an increased risk of travel-related illness. Changes in global mobility, travel patterns, and inter-regional travel led to reappraisal of the classic definition of the term VFR. METHODS: The peer-reviewed literature was accessed through electronic searchable sites (PubMed/Medline, ProMED, GeoSentinel, TropNetEurop, Eurosurveillance) using standard search strategies for the literature related to visiting friends/relatives, determinants of health, and travel. We reviewed the historic and current use of the definition of VFR traveler in the context of changes in population dynamics and mobility. RESULTS: The term "VFR" is used in different ways in the literature making it difficult to assess and compare clinical and research findings. The classic definition of VFR is no longer adequate in light of an increasingly dynamic and mobile world population. CONCLUSIONS: We propose broadening the definition of VFR travelers to include those whose primary purpose of travel is to visit friends or relatives and for whom there is a gradient of epidemiologic risk between home and destination, regardless of race, ethnicity, or administrative/legal status (eg, immigrant). The evolution and application of this proposed definition and an approach to risk assessment for VFR travelers are discussed.

Health information given by Swiss travel agencies.

BACKGROUND: Many of the 1 million Swiss traveling to tropical or subtropical countries book their trip through travel agencies every year. These agencies are thus an important source of information about malaria and other important health risks and little is known about the appropriate health information provided by these. METHOD: A study was conducted to assess health-related information in members of the Swiss Federation of Travel Agencies in the metropolitan area of Zurich, Switzerland. A covert investigator (F.M.S.) visited these agencies and requested information on a package holiday for 2 or 3 weeks to Kenya. Following an in-person interview, the investigator recorded any health-related information provided on a pretested form. If none was mentioned, the agent was prompted using a standardized procedure. RESULTS: A total of 88 agencies were visited. Spontaneous health advice was given in 44% of all visits. After prompting, 99% of all travel agents mentioned preventive measures against malaria, but only 69% indicated the need for vaccinations against other diseases. Spontaneous advice on malaria risk and vaccinations was better than advice given upon prompting. One fifth of all travel agents neither mentioned malaria prevention measures spontaneously nor recommended seeing a health specialist. CONCLUSIONS: Overall, travel medicine knowledge of travel agents in the Zurich area needs improvement as many tended to draw attention to health risks only when prompted. Attitude, personal knowledge, and experience of individual travel agents were key to the health information given. Up-to-date and readily available information on health risks should be provided to travel agencies and structured training given in collaboration with health professionals.

Immunogenicity of booster vaccination with a virosomal hepatitis A vaccine after primary immunization with an aluminum-adsorbed hepatitis A vaccine.

BACKGROUND: Increasing numbers of individuals are traveling to areas of high hepatitis A endemicity and require immunization against the hepatitis A virus (HAV). The option of using a virosomal, aluminum-free, HAV vaccine (Epaxal) for booster immunization following primary vaccination with an aluminum-adsorbed vaccine has been assessed. METHODS: In total, 142 healthy subjects, 79 men and 63 women, aged 12 to 72 years, were injected intramuscularly with a booster dose of Epaxal (0.5 mL containing < or =500 RIA units of HAV antigen) 6 to 24 months after primary vaccination with Havrix (0.5 or 1.0 mL containing 720 or 1440 ELISA units of HAV antigen, respectively, adsorbed onto aluminum hydroxide). Anti-HAV antibody titers were measured on days 0 and 28 by an enzyme immunoassay. Adverse events were recorded for 1 month postinjection. RESULTS: Overall, 98/118 subjects (83%) with no serologic evidence of past HAV infection were still seroprotected at enrolment (anti-HAV antibody titer < or = 20 mIU/mL). The seroprotection rate was 87% in those primed with Havrix 1440 6 to 12 months earlier (n=93) and 60% in those primed < or =12 months before enrolment (n=20, mean 16 months). The geometric mean anti-HAV antibody titer increased from 65 mIU/mL at day 0 to 1,722 mIU/mL at day 28 after a single booster dose with Epaxal in evaluable subjects who were primarily vaccinated with either a single dose of Havrix 1440 (n=111) or two separate doses of Havrix 720 (n=4). All subjects were seroprotected at day 28, and 98% showed at least a four-fold increase in anti-HAV antibody titer. Epaxal was well tolerated and no serious adverse events were reported. At day 28, the tolerability of the vaccination was judged as either "very good" or "good" by 96% of vaccinees and by all investigators. CONCLUSION: Epaxal can be successfully used to boost immunization following primary vaccination with an aluminum-adsorbed vaccine, and is well tolerated.