Establishment of a clinical algorithm for the diagnosis of P. falciparum malaria in children from an endemic area using a Classification and Regression Tree (CART) model

Die Weltgesundheitsorganisation WHO schätzte die Zahl der an Malaria erkrankten Menschen im Jahr 2009 auf weltweit 225 Millionen. Auf dem afrikanischen Kontinent betrafen 85% der durch Malaria verursachten Todesfälle Kinder unter fünf Jahren. Obwohl die Inzidenzen der P. falciparum-Malaria in einigen Teilen des subsaharischen Afrika sinken und andere Erkrankungen mit ähnlichen Symptomen wie denen der Malaria an Bedeutung gewinnen, ist eine vorsorgliche medikamentöse Behandlung im Verdachtsfall weiterhin üblich. Ziel dieser Arbeit ist die Generierung eines auf das Lebensalter bezogenen klinischen Algorithmus, der mit einfachen klinischen Symptomen die Diagnose einer P. falciparum - Parasitämie ermöglicht. Die Studie wurde in einem ländlichen Krankenhaus in der Ashanti-Region in Ghana durchgeführt, welche über das ganze Jahr hinweg holoendemisch für Malaria ist. Insgesamt wurden 5447 ambulante Besuche von 3641 Patienten im Alter zwischen 2-60 Monaten analysiert. Alle Kinder wurden von einem Pädiater klinisch untersucht und es wurden ein kleines Blutbild sowie ein Malariaausstrich (‘Dicker Tropfen’) angefertigt. Mit Hilfe einesClassification and Regression Tree (CART) wurde ein klinischer Entscheidungsbaum für die Prädiktion einer Plasmodium-Parasitämie generiert und prädiktive Werte für alle erfassten Symptome berechnet. Eine Parasitämie wurde bei Kindern im Alter von 2-12 Monaten mit einer Prävalenz von 13.8% und bei Kindern im Alter zwischen 12 und 60 Monatenmit einer Prävalenz von 30.6% gefunden. Das CART-Modell ergab altersabhängige Unterschiede in der Fähigkeit der Variablen eine Parasitämie vorherzusagen. Während sich bei Kindern im Alter zwischen 2 und 12 Monaten die „palmare Blässe“ als das wichtigste Symptom herausstellte, gewannen die Variablen „Fieber in der Anamnese“ und „erhöhte Körpertemperatur ≥ 37.5°C“ bei Kindern im Alter zwischen 12 und 60 Monaten an Bedeutung. Die Variable „palmare Blässe“ war bei Kindern jedes Alters signifikant (p<0.001) mit niedrigeren Hämoglobinwerten assoziiert. Im Vergleich zum Algorithmus des Integrated Management of Childhood Illness (IMCI) hatte das CART-Modell eine deutlich höhere Spezifität sowie einen höheren positiven prädiktiven Wert für die Vorhersage einer Parasitämie. Die Anwendung von altersbezogenen Algorithmen erhöht die Spezifität der Vorhersage einer P. falciparum - Parasitämie. Selbst in einer Population mit einer hohen Prävalenz an Anämie ermöglicht der prädiktive Wert der „palmaren Blässe“ eine Erkennung von signifikant geringeren Hb-Werten. Die Bedeutung der „palmaren Blässe“ sollte daher in der Schulung von Gesundheitshelfern hervorgehoben werden. Mangels ausreichender Sensitivität kann allerdings weder auf Basis des besten Algorithmus noch mit „palmarer Blässe“ als einzelnem klinischem Zeichen eine Therapieentscheidung getroffen werden. Sie sind daher kein Ersatz für eine vorsorgliche medikamentöse Behandlung und einen Erregernachweis

Predictive Value of Fever and Palmar Pallor for P. falciparum Parasitaemia in Children from an Endemic Area

INTRODUCTION: Although the incidence of Plasmodium falciparum malaria in some parts of sub-Saharan Africa is reported to decline and other conditions, causing similar symptoms as clinical malaria are gaining in relevance, presumptive anti-malarial treatment is still common. This study traced for age-dependent signs and symptoms predictive for P. falciparum parasitaemia. METHODS: In total, 5447 visits of 3641 patients between 2-60 months of age who attended an outpatient department (OPD) of a rural hospital in the Ashanti Region, Ghana, were analysed. All Children were examined by a paediatrician and a full blood count and thick smear were done. A Classification and Regression Tree (CART) model was used to generate a clinical decision tree to predict malarial parasitaemia a7nd predictive values of all symptoms were calculated. RESULTS: Malarial parasitaemia was detected in children between 2-12 months and between 12-60 months of age with a prevalence of 13.8% and 30.6%, respectively. The CART-model revealed age-dependent differences in the ability of the variables to predict parasitaemia. While palmar pallor was the most important symptom in children between 2-12 months, a report of fever and an elevated body temperature of ≥37.5°C gained in relevance in children between 12-60 months. The variable palmar pallor was significantly (p<0.001) associated with lower haemoglobin levels in children of all ages. Compared to the Integrated Management of Childhood Illness (IMCI) algorithm the CART-model had much lower sensitivities, but higher specificities and positive predictive values for a malarial parasitaemia. CONCLUSIONS: Use of age-derived algorithms increases the specificity of the prediction for P. falciparum parasitaemia. The predictive value of palmar pallor should be underlined in health worker training. Due to a lack of sensitivity neither the best algorithm nor palmar pallor as a single sign are eligible for decision-making and cannot replace presumptive treatment or laboratory diagnosis

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Response to fever and utilization of standby emergency treatment (SBET) for malaria in travellers to Southeast Asia: a questionnaire-based cohort study

Background: Guidelines in several European countries recommend standby emergency treatment (SBET) for travellers to regions with low or medium malaria transmission instead of continuous chemoprophylaxis: travellers are advised to seek medical assistance within 24 h in case of fever and to self-administer SBET only if they are not able to consult a doctor within the time period specified. Data on healthcare-seeking behaviour of febrile travellers and utilization of SBET is however scarce as only two studies were performed in the mid-1990s. Since tourism is constantly increasing and malaria epidemiology has dramatically changed in the meantime more knowledge is urgently needed. Methods: Some 876 travellers to destinations in South and Southeast Asia with low or medium malaria transmission were recruited in the travel clinic of the University Medical Center Hamburg-Eppendorf. Demographic and travel-related data were collected by using questionnaires. Pre-travel advice was carried out and SBET was prescribed in accordance to national guidelines. Post-travel phone interviews were performed to assess health incidents during travel and individual responses of travellers to febrile illness. Results: Out of 714 patients who were monitored, 130 (18%) reported onset of fever during travel or 14 days after return. Of those travellers who reported fever, 100 (80%) carried SBET during travel. The vast majority of 79 (79%) febrile travellers who carried SBET did not seek medical assistance. Overall, 14 (14%) febrile patients who carried SBET and six (20%) patients who did not carry SBET took the correct measure (doctor visit or timely SBET administration) as a response to febrile illness, respectively. Only two travellers self-administered SBET, but both of them applied the wrong regimen. Conclusions: In view of declining malaria transmission and improving medical infrastructure in most countries of Southeast Asia and obvious obstacles concerning SBET as shown in this study the current strategy should be re-evaluated. Pre-travel advice concerning malaria in SEA should focus on appropriate mosquito bite protection and clearly emphasize the need to see a doctor within 24 h after onset of fever

High prevalence of asymptomatic malaria infections in adults, Ashanti Region, Ghana, 2018

Background!#!Ghana is among the high-burden countries for malaria infections and recently reported a notable increase in malaria cases. While asymptomatic parasitaemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce, and usually focus on children and on non-falciparum species. The present study aims to assess the prevalence of asymptomatic Plasmodium falciparum and non-falciparum infections in Ghanaian adults in the Ashanti region during the high transmission season.!##!Methods!#!Asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium species by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR. For all Plasmodium ovale infections additional sub-species identification was performed.!##!Results!#!Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with P. ovale. The sub-species P. ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with P. falciparum.!##!Conclusions!#!Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with P. malariae, P. o. curtisi and P. o. wallikeri

Signs and symptoms and their association with <i>P. falciparum</i> parasitaemia in children.

a<p>To be positive for this (inverse) variable patients must not present <i>malnourished condition</i>.</p>b<p>To be positive for this (inverse) variable patients must not present <i>skin abnormalities</i>, <i>skin rash</i>, <i>skin depigmentation</i> and <i>other skin problem</i>.</p>c<p>To be positive for this (inverse) variable patients must not present <i>vomiting</i> and <i>diarrhoea</i>.</p>d<p>To be positive for this (inverse) variable patients must not present <i>respiratory distress, breathing difficulties, fast breathing, deep breathing, chest indrawing, running nose</i>, blocked nose and <i>cough</i>.</p>e<p>CI: 95% Confidence interval.</p

Enrollment and exclusion of patients for analysis.

<p>^a A patient is defined as an individual visiting the OPD. ^b Case report forms must have information for each variable in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036678#pone-0036678-t002" target="_blank">Table 2</a> available.</p

Distribution of haemoglobin-values in patients of different ages with and without palmar pallor.

<p>p-value was calculated assuming a Student's t distribution.</p

Classification and comparison of CART model and IMCI algorithm.

a<p>IMCI-algorithm for identification of children with malaria in high-risk areas: Fever by history of fever or feeling hot/elevated body temperature of ≥37.5°C on admission and/or some palmar pallor.</p>b<p>CART-model: For calculation only those variables were used, which were included in the CART-analysis for the certain age group.</p>c<p>PPV = Positive predictive value.</p>d<p>NPV = Negative predictive value.</p