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Background: Malaria is the parasitic disease with the highest morbimortality worldwide. The World Health Organization (WHO) estimates that there were approximately 249 million cases in 2022, of which 3.4% were in Angola. Diagnosis is based on parasite identification by microscopy examination, antigen detection, and/or molecular tests, such as polymerase chain reaction (PCR). This study aimed to evaluate the usefulness of real-time PCR as a diagnostic method for malaria in an endemic area (Cubal, Angola)., Methods: A cross-sectional study was carried out at the Hospital Nossa Senhora da Paz in Cubal, Angola, including 200 patients who consulted for febrile syndrome between May and July 2022. From each patient, a capillary blood sample was obtained by finger prick for malaria field diagnosis [microscopy and rapid diagnostic test (RDT)] and venous blood sample for real-time PCR performed at the Hospital Universitario Vall d'Hebron in Barcelona, Spain. Any participant with a positive result from at least one of these three methods was diagnosed with malaria., Results: Of the 200 participants included, 54% were female and the median age was 7 years. Malaria was diagnosed by at least one of the three techniques (microscopy, RDT, and/or real-time PCR) in 58% of the participants, with RDT having the highest percentage of positivity (49%), followed by real-time PCR (39.5%) and microscopy (33.5%). Of the 61 discordant samples, 4 were only positive by microscopy, 13 by real-time PCR, and 26 by RDT. Plasmodium falciparum was the most frequent species detected (90.63%), followed by P. malariae (17.19%) and P. ovale (9.38%). Coinfections were detected in ten participants (15.63%): six (60%) were caused by P. falciparum and P. malariae, three (30%) by P. falciparum and P. ovale, and one (10%) triple infection with these three species. In addition, it was observed that P. falciparum and P. malariae coinfection significantly increased the parasite density of the latter., Conclusions: RDT was the technique with the highest positivity rate, followed by real-time PCR and microscopy. The results of the real-time PCR may have been underestimated due to suboptimal storage conditions during the transportation of the DNA eluates. However, real-time PCR techniques have an important role in the surveillance of circulating Plasmodium species, given the epidemiological importance of the increase in non-falciparum species in the country, and can provide an estimate of the intensity of infection., (© 2024. The Author(s).)

Acute febrile illness (AFI) is a common reason for healthcare seeking and hospitalization in Sub-Saharan Africa and is often presumed to be malaria. However, a broad range of pathogens cause fever, and more comprehensive data on AFI etiology can improve clinical management, prevent unnecessary prescriptions, and guide public health interventions. We conducted surveillance for AFI (temperature ≥38.0°C <14 days duration) among hospitalized patients of all ages at four sites in Kenya (Nairobi, Mombasa, Kakamega, and Kakuma). For cases of undifferentiated fever (UF), defined as AFI without diarrhea (≥3 loose stools in 24 hours) or lower respiratory tract symptoms (cough/difficulty breathing plus oxygen saturation <90% or [in children <5 years] chest indrawing), we tested venous blood with real-time PCR-based TaqMan array cards (TAC) for 17 viral, 8 bacterial, and 3 protozoal fever-causing pathogens. From June 2017 to March 2019, we enrolled 3,232 AFI cases; 2,529 (78.2%) were aged <5 years. Among 3,021 with outcome data, 131 (4.3%) cases died while in hospital, including 106/2,369 (4.5%) among those <5 years. Among 1,735 (53.7%) UF cases, blood was collected from 1,340 (77.2%) of which 1,314 (98.1%) were tested by TAC; 715 (54.4%) had no pathogens detected, including 147/196 (75.0%) of those aged <12 months. The most common pathogen detected was Plasmodium, as a single pathogen in 471 (35.8%) cases and in combination with other pathogens in 38 (2.9%). HIV was detected in 51 (3.8%) UF cases tested by TAC and was most common in adults (25/236 [10.6%] ages 18-49, 4/40 [10.0%] ages ≥50 years). Chikungunya virus was found in 30 (2.3%) UF cases, detected only in the Mombasa site. Malaria prevention and control efforts are critical for reducing the burden of AFI, and improved diagnostic testing is needed to provide better insight into non-malarial causes of fever. The high case fatality of AFI underscores the need to optimize diagnosis and appropriate management of AFI to the local epidemiology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Introduction: The scarcity of epidemiological data on acute febrile illnesses from South Asia impairs evidence-based clinical decision-making. Our study aimed to explore the etiological spectrum of short-duration fever in patients admitted to a tertiary care hospital in West Bengal, India., Methods: We conducted a cross-sectional study from May 2021 to April 2022 involving 150 adult patients presenting with a fever lasting less than two weeks at Burdwan Medical College and Hospital (West Bengal, India). We performed comprehensive clinical assessments, including microbiological, serological, and other specific investigations, to identify the causes of the fever., Results: The demographic profile predominantly included individuals aged 21-40 years, with a male-to-female ratio of 1.9:1; 60.7% of participants were from rural areas. The primary etiological agents identified were scrub typhus (25.3%), dengue (15.3%), and enteric fever (13.3%). Notably, 80% of patients presented with non-localizing symptoms, while 14.7% had respiratory symptoms. Blood cultures pinpointed Salmonella typhi and Staphylococcus aureus in a minority of cases (3.3%); malaria, primarily Plasmodium vivax, was diagnosed in 12% of the cases., Conclusion: Our findings highlight the complexity of diagnosing short-duration fevers, dominated by a wide range of etiological agents, with a notable prevalence of scrub typhus. These results underscore the urgent need for enhanced diagnostic facilities, including the availability of scrub typhus testing at primary healthcare centers. We recommend empirical doxycycline therapy for suspected cases and emphasize the need for further research to develop management guidelines for acute febrile illnesses. This study also highlights the importance of raising both community and clinician awareness to prevent irrational antibiotic use., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Diagnosing the causative agent of febrile illness in resource-limited countries is a challenge in part due to lack of adequate diagnostic infrastructure to confirm cause of infection. Most febrile illnesses (>60%) are non-malarial, with a significant proportion being zoonotic and likely from animal origins. To better characterize the pathways for zoonotic disease transmission and control in vulnerable communities, adequate information on the communities' experiences and lexicon describing fever, and their understanding and perceptions of risk pathways is required. We undertook an ethnographic study to understand behaviors, exposures, and attitudes toward fever at the community level. Our hope is to better elucidate areas of priority surveillance and diagnostic investment. A focused ethnography consisting of participant observation, informal conversations, 4 barazas (community meetings), and formal ethnographic interviews (13 Focus group discussions and 17 Key informant interviews) was conducted between April and November 2015 in Kasese and Hoima Districts in Uganda. Perception of illness and associated risk factors was heavily influenced by the predominant livelihood activity of the community. The term "fever" referred to multiple temperature elevating disease processes, recognized as distinct pathological occurrences. However, malaria was the illness often cited, treated, or diagnosed both at the health facilities and through self-diagnosis and treatment. As expected, fever is as an important health challenge affecting all ages. Recognition of malarial fever was consistent with a biomedical model of disease while non-malarial fevers were interpreted mainly through ethno etiological models of explanation. These models are currently being used to inform education and prevention strategies and treatment regimens toward the goal of improving patients' outcomes and confidence in the health system. Development of treatment algorithms that consider social, cultural, and economic contexts, especially where human-animal interaction is prevalent, should factor animal exposure and zoonotic illnesses as important differentials., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Most children in the United States who visit the emergency department (ED) with fever have minor illnesses not requiring treatment or hospitalization. However, when a child has recently immigrated or traveled abroad, internationally acquired severe systemic infections (ISSIs) must be considered. We sought to describe children who have traveled internationally and present to the ED with a complaint of fever and to determine risk factors associated with ISSIs in these patients., Methods: We conducted a retrospective study of children younger than 18 years who presented to 2 pediatric EDs in Bronx, NY (June 2007 to May 2017). Patients were included if they had both fever within 24 hours and international travel within 30 days. We compared groups using bivariate analyses and created a prediction model for ISSIs using multivariable logistic regression., Results: Of the 353 children included, 44 (12%) had ISSI: 25 (57%), malaria; 6 (14%), dengue; and 13 (30%), bacteremia. Eight (18%) of those with ISSI presented with fever to another medical provider in the week prior but did not receive bloodwork. Four variables were independently associated with ISSIs: headache (odds ratio [OR], 21.7; 95% confidence interval [CI], 6.8-69.3), travel to Africa or Asia (OR, 18.8; 95% CI, 4.8-73.2), platelets of 150,000/μL or less (OR, 15.1; 95% CI, 4.7-48.6), and alanine aminotransferase level of 30 IU/L or greater (OR, 8.9; 95% CI, 3.1-25.3)., Conclusions: Children who travel internationally and present with fever upon return are at substantial risk for developing ISSIs. The diagnosis of ISSIs is often overlooked, but certain risk factors have the potential to aid clinicians., Competing Interests: Disclosure: There are no conflicts of interests to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: In 2010, WHO published guidelines emphasising parasitological confirmation of malaria before treatment. We present data on changes in fever case management in a low malaria transmission setting of northern Tanzania after 2010., Methods: We compared diagnoses, treatments and outcomes from two hospital-based prospective cohort studies, Cohort 1 (2011-2014) and Cohort 2 (2016-2019), that enrolled febrile children and adults. All participants underwent quality-assured malaria blood smear-microscopy. Participants who were malaria smear-microscopy negative but received a diagnosis of malaria or received an antimalarial were categorised as malaria over-diagnosis and over-treatment, respectively., Results: We analysed data from 2098 participants. The median (IQR) age was 27 (3-43) years and 1047 (50.0%) were female. Malaria was detected in 23 (2.3%) participants in Cohort 1 and 42 (3.8%) in Cohort 2 (p = 0.059). Malaria over-diagnosis occurred in 334 (35.0%) participants in Cohort 1 and 190 (17.7%) in Cohort 2 (p < 0.001). Malaria over-treatment occurred in 528 (55.1%) participants in Cohort 1 and 196 (18.3%) in Cohort 2 (p < 0.001). There were 30 (3.1%) deaths in Cohort 1 and 60 (5.4%) in Cohort 2 (p = 0.007). All deaths occurred among smear-negative participants., Conclusion: We observed a substantial decline in malaria over-diagnosis and over-treatment among febrile inpatients in northern Tanzania between two time periods after 2010. Despite changes, some smear-negative participants were still diagnosed and treated for malaria. Our results highlight the need for continued monitoring of fever case management across different malaria epidemiological settings in sub-Saharan Africa., (© 2021 John Wiley & Sons Ltd.)

Dengue virus (DENV) causes a spectrum of diseases ranging from asymptomatic, mild febrile to a life-threatening illness: dengue hemorrhagic fever. The main clinical symptom of dengue is fever, similar to that of malaria. The prevalence of dengue virus infection, alone or in association with other endemic infectious diseases in children in Cameroon is unknown. The aim of this study was to determine the prevalence of dengue, malaria and HIV in children presenting with fever and associated risk factors. Dengue overall prevalence was 20.2%, Malaria cases were 52.7% and HIV cases represented 12.6%. The prevalence of dengue-HIV co-infection was 6.0% and that of Malaria-dengue co-infection was 19.5%. Triple infection prevalence was 4.3%. Dengue virus infection is present in children and HIV-Dengue or Dengue- Malaria co-infections are common. Dengue peak prevalence was between August and October. Sex and age were not associated with dengue and dengue co-infections. However, malaria as well as HIV were significantly associated with dengue (P = 0.001 and 0.028 respectively). The diagnosis of dengue and Malaria should be carried out routinely for better management of fever., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study aims to identify significant symptoms and nonsymptom-related factors for malaria diagnosis in endemic regions of Indonesia., Methods: Medical records are collected from patients suffering from malaria and other febrile diseases from public hospitals in endemic regions of Indonesia. Interviews with eight Indonesian medical doctors are conducted. Feature selection and machine learning techniques are used to develop malaria classifiers for identifying significant symptoms and nonsymptom-related factors., Results: Seven significant symptoms (duration of fever, headache, nausea and vomiting, heartburn, severe symptom, dizziness, and joint pain) and patients' history of malaria as a nonsymptom-related factor contribute most to malaria diagnosis. As a symptom, fever duration is more significant than temperature or fever for distinguishing malaria from other febrile diseases. Shivering, fever, and sweating (known to indicate malaria presence in Indonesia) are shown to be less significant than other symptoms in endemic regions., Conclusions: Three most suitable malaria classifiers have been developed to identify the significant features that can be used to predict malaria as distinct from other febrile diseases. With extensive experiments on the classifiers, the significant features identified can help medical doctors in the clinical diagnosis of malaria and raise public awareness of significant malaria symptoms at early stages., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: In low-resource settings, treatment is often given empirically without knowledge of the aetiology due to a lack of diagnostics. In the search for reliable rapid tests to guide treatment work-up, this study was performed to determine whether two biomarkers could differentiate bacterial from non-bacterial infections in acute febrile patients., Methods: Adults with acute fever were recruited at a referral hospital in Ethiopia. The QuikRead Go test was used to quantify C-reactive protein (qCRP) and the FebriDx test was used for combined qualitative detection of the bacterial CRP marker with myxovirus resistance protein A (MxA), a viral biomarker., Results: Of the 200 patients included in this study, most presented with 2-3 days of fever, headache, and joint pain. Antibiotics were prescribed for 83.5% and antimalarials for 36.5%, while a bacterial infection was only confirmed in 5% and malaria in 11%. The median qCRP level for confirmed bacterial infections was 128 mg/l. The FebriDx and QuikRead Go test had an overall agreement of 72.0%., Conclusions: An over-prescription of antibiotics for febrile patients was observed, even for those with low CRP levels and without a confirmed bacterial infection. The added value of the FebriDx was limited, while the combined use of rapid tests for qCRP and malaria should be considered for the management of acute febrile illness and antibiotic stewardship., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The diagnosis of non-malarial aetiologies, which now represent the majority of febrile illnesses, has remained problematic in settings with limited laboratory capacity. We aimed to describe common aetiologies of acute febrile illness among children in a setting where malaria transmission has declined., Methods: A prospective cross-sectional study was conducted among children aged at least 2 months and under 13 years presenting with fever (temperature of ≥37.5 °C or a history of fever in the past 48 h) to Hawassa Comprehensive Specialized Hospital, southern Ethiopia, from May 2018 through February 2019. Clinical and demographic data were gathered for consecutive participants, and malaria microscopy, HIV testing, and blood and urine cultures were performed regardless of clinical presentation. Additionally, stool analyses (culture and rotavirus/adenovirus RDT) and throat swab for group A Streptococcus (GAS) and urine Streptococcus pneumoniae were performed by RDTs for children with specific conditions. The antimicrobial susceptibility of bacterial isolates was determined using disc diffusion method., Results: During the study period 433 children were recruited, median age 20 months (range, 2 months - 12 years) and 178 (41.1%) female. Malaria was diagnosed in 14 (3.2%) of 431 children, and 3 (0.7%) had HIV infection. Bacteraemia or fungaemia was detected in 27 (6.4%) of 421 blood cultures, with Staphylococcus aureus isolated in 16 (3.8%). Urinary tract infections (UTIs) were detected in 74 (18.4%) of 402, with Escherichia coli isolated in 37 (9.2%). Among 56 children whose stool specimens were tested, 14 (25%) were positive for rotavirus, 1 (1.8%) for Salmonella Paratyphi A, and 1 (1.8%) for Shigella dysenteriae. Among those with respiratory symptoms, a throat swab test for GAS and urine test for S. pneumoniae were positive in 28 (15.8%) of 177 and 31 (17.0%) of 182, respectively. No test was positive for a pathogen in 266 (61.4%) of 433 participants. Bacterial isolates were frequently resistant to ampicillin, trimethoprim-sulfamethoxazole, tetracycline, and amoxicillin and clavulanic acid., Conclusion: Our results showed low proportions of malaria and bacteraemia among febrile children. In contrast, the frequent detection of UTI emphasize the need to support enhanced diagnostic capacity to ensure appropriate antimicrobial intervention.

Background: The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity., Methods: Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence., Results: Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001)., Conclusions: Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.

Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim-sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.

Background: Early diagnosis and treatment of malaria symptoms reduces the risk of severe complication and malaria transmission. However, delay in malaria diagnosis and treatment is a major public health problem in India. The primary aim of the study was to determine cut-off for the delay in seeking treatment of fever, and the secondary aim was to identify the factors associated with delay in malaria-endemic areas of Assam, Northeast India., Methods: The present study analysed data from two prior cross-sectional surveys (community- and hospital-based) that was conducted to study the health-seeking behaviour of people residing in high malaria-endemic areas of Assam, Northeast India. The hospital-based survey data were used to determine optimal cut-off for the delay in reporting, and further, used to identify the factors associated with delay using community-based data., Results: Mean age of fever cases was similar in both community- and hospital-based surveys (23.1 years vs 24.2 years, p = 0.229). Delay in reporting fever was significantly higher among hospital inpatients compared to community-based fever cases (3.6 ± 2.1 vs 4.0 ± 2.6 days; p = 0.006). Delay of > 2 days showed higher predictive ability (sensitivity: 96.4%, and ROC area: 67.5%) compared to other cut-off values (> 3, > 4, and > 5 days). Multivariable logistic regression analysis revealed that the adjusted odds ratio (aOR) of delay was significantly higher for people living in rural areas (1.52, 95%CI: 1.11-2.09), distance (> 5 km) to health facility (1.93, 95%CI: 1.44-2.61), engaged in agriculture work (2.58, 95%CI: 1.97-3.37), and interaction effect of adult male aged 20-40 years (1.71, 95%CI: 1.06-2.75)., Conclusion: The delay (> 2 days) in seeking treatment was likely to be twice among those who live in rural areas and travel > 5 km to assess health care facility. The findings of the study are useful in designing effective intervention programmes for early treatment of febrile illness to control malaria.

Like most malaria-endemic countries, Mozambique relies on tabulation of confirmed malaria test-positive febrile patients to track incidence of malaria. However, this approach is potentially biased by incidental malaria parasitemia in patients with fever of another etiology. We compared pan- Plasmodium aldolase and lactate dehydrogenase and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) antigen concentrations measured using a laboratory bead-based assay of samples collected from 1,712 febrile and afebrile patients of all ages in Maputo, Zambézia, and Cabo Delgado provinces. We used a Bayesian latent class model to estimate the proportion of malaria-attributable fevers in malaria test-positive febrile patients. Depending on the antigen, estimated rates of malaria-attributable fever in malaria test-positive febrile patients were 100% in Maputo, 33-58% in Zambézia, and 63-74% in Cabo Delgado. Our findings indicate that most malaria test-positive febrile patients in the three provinces of Mozambique had a fever that was likely caused by the concurrent malaria infection. Counting malaria test-positive febrile patients for estimation of malaria incidence appears to be appropriate in this setting.

The epidemiology of febrile illness etiologies is under-explored in resource-poor settings. Establishing a local repertory of microorganisms circulating in blood of febrile and afebrile people is important for physicians. Blood was collected from 428 febrile and 88 afebrile children in Makokou (Gabon) and analyzed using polymerase chain reaction. Plasmodium spp. were the pathogens, which were most detected in febrile children (69.6%; 298/428) and in afebrile children (31.8%; 28/88) ( P < 0.0001). Plasmodium falciparum was the most prevalent species in both febrile and afebrile children (66.8% and 27.3%, respectively). No differences were observed between febrile and afebrile children for Plasmodium malariae and Plasmodium ovale (8.2% versus 10.2% and 3.3% versus 3.4%, respectively). Triple infection with P. falciparum , P. malariae , and P. ovale was also detected in 1% of febrile children (4/428). Filariasis due to Mansonella perstans was detected in 10 febrile patients (2.3%), whereas Loa loa was detected in both febrile and afebrile children (1.4% and 2.3%, respectively). Bacterial DNA was detected in only 4.4% (19/428) of febrile children, including 13 (68.4%) who were coinfected with at least one Plasmodium species. These were Haemophilus influenzae (1.6%, 7/428), Streptococcus pneumoniae and Staphylococcus aureus (1.2%, 5/428), and Rickettsia felis (0.9%, 4/428). Coxiella burnetii , Bartonella spp., Borrelia spp., Tropheryma whipplei , Anaplasma spp., Leptospira spp., Streptococcus pyogenes , and Salmonella spp. were not detected. This study also highlights the over-prescription and the overuse of antibiotics and antimalarials. Overall, malaria remains a major health problem in Makokou. Malaria control measures must be reconsidered in this region.

Background: The relative contribution of bacterial infections to febrile disease is poorly understood in many African countries due to diagnostic limitations. This study screened pediatric and adult patients attending 4 healthcare facilities in Ibadan, Nigeria, for bacteremia and malaria parasitemia., Methods: Febrile patients underwent clinical diagnosis, malaria parasite testing, and blood culture. Bacteria from positive blood cultures were isolated and speciated using biochemical and serological methods, and Salmonella subtyping was performed by polymerase chain reaction. Antimicrobial susceptibility was tested by disk diffusion., Results: A total of 682 patients were recruited between 16 June and 16 October 2017; 467 (68.5%) were <18 years of age. Bacterial pathogens were cultured from the blood of 117 (17.2%) patients, with Staphylococcus aureus (69 [59.0%]) and Salmonella enterica (34 [29.1%]) being the most common species recovered. Twenty-seven (79.4%) of the Salmonella isolates were serovar Typhi and the other 7 belonged to nontyphoidal Salmonella serovarieties. Thirty-four individuals were found to be coinfected with Plasmodium falciparum and bacteria. Five (14.7%) of these coinfections were with Salmonella, all in children aged <5 years. Antimicrobial susceptibility testing revealed that most of the Salmonella and Staphylococcus isolates were multidrug resistant., Conclusions: The study demonstrates that bacteria were commonly recovered from febrile patients with or without malaria in this location. Focused and extended epidemiological studies are needed for the introduction of typhoid conjugate vaccines that have the potential to prevent a major cause of severe community-acquired febrile diseases in our locality., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Reducing the burden of malaria highly depends on access to prompt and effective malaria diagnosis and treatment. The aim of this study was to identify challenges affecting prompt access to effective uncomplicated malaria case management in children below 10 years old in rural primary health care facilities in Malawi., Methods: A cross sectional health facility survey was conducted in six primary health facilities in Chikhwawa district, Malawi. Officers-in-charge of health facilities were interviewed on availability of staff, supplies and drugs. All consecutive children presenting at the facility with fever or suspected malaria, aged 6 months to 10 years old, were eligible to participate in exit interviews. Exit interviews with participants' guardians assessed duration of illness, demographic information and distance travelled. Adherence to recommended malaria case management guidelines included performing malaria rapid diagnostic tests (mRDTs) in children with fever or suspected malaria and prescribing recommended weight-based dose of artemether-lumefantrine (AL) when mRDT was positive. Multivariate logistic regression was used to determine factors associated with prompt care seeking within 24 h of onset of illness., Results: Health facilities were staffed by at least two health workers. Of 265 children screened, nine were excluded due to severe illness. Twenty-one percent of children presenting at a health facility with fever were not tested for malaria. Adherence to positive and negative mRDT results for those tested was 99.4, 95% CI [98.1-100] and 97, 95% CI [88.9-100], respectively. AL was prescribed as recommended by weight in 152 children (92.2%). Temporary stock outs of AL occurred in five of six facilities. In total, 146 (57, 95% CI [52.7-64.1]) guardians of patients sought care within 24 h after fever onset. Children aged 5 to 10 years were less likely to present within 24 h of fever onset than children below 5 years of age (unadjusted odds ratio 0.40, 95% CI [0.2-0.7])., Conclusion: Adherence to malaria diagnosis and treatment guidelines was high. However, delayed care seeking and stock outs may affect prompt and effective malaria case management. Further qualitative work is required to determine, and address factors associated with delay in care seeking for fever.

Fever is one of the most common symptoms of pediatric illnesses; it is an important early symptom of malaria. Fever had served as the entry point for presumptive treatment of malaria among children in Nigerian. Appropriate HSB is important when seeking treatment for fever among under-five children; this will help for better prognosis because treatment will be initiated early. This study attempted to identify caregiver's HSB for under-five children with fever. A cross-sectional study was conducted in Imo-State, Nigeria. Appropriate HSB was operationally defined as seeking treatment from health facility within 24 h of fever. Data were obtained using pretested self-administered questionnaire. Data were analyzed using SPSS version 22. Simple and multiple logistic regression were used to determine predictors of appropriate HSB. A total of 559 eligible respondents were recruited; 103 (18.6%) caregivers had appropriate HSB. The predictors of HSB are being male child (aOR = 2.760; 95% CI:1.536-4.958), the age of child younger than 27 months (aOR = 2.804; 95% CI:1.485-5.295), employed caregivers (aOR = 1.882; 95% CI:1.014-3.493), number of household members (aOR = 2.504; 95% CI:1.464-4.283), and caregivers who decided to seek treatment at early stage (aOR = 7.060; 95% CI:1.616-30.852). Only 18.6% caregivers practiced appropriate HSB for fever cases among under-five children. It is essential to educate caregivers and emphasise on early treatment of fever and appropriate use of health facilities for fever. The findings will be used to improve intervention at the community level and will be compared with follow-up data to evaluate their effectiveness.

The increase in international travel, the growing presence of arbovirus vectors in our country, and notifications of haemorrhagic fever such as the current outbreak of Ebola in D.R. Congo and the cases of Crimea-Congo haemorrhagic fever in our country have again cast the spotlight on tropical diseases Isolating suspected cases of highly contagious and lethal diseases must be a priority (Haemorrhagic fever, MERS-CoV). Assessing the patient, taking a careful medical history based on epidemiological aspects of the area of origin, activities they have carried out, their length of stay in the area and the onset of symptoms, will eventually help us, if not to make a definitive diagnosis, at least to exclude diseases that pose a threat to these patients. Malaria should be ruled out because of its frequency, without forgetting other common causes of fever familiar to emergency doctors., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Background: Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis., Methodology: We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections., Results: Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue-caused by DENV-1 and/or DENV-2 -and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment., Discussion: Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will-ultimately and hopefully-improve the clinical care of outpatients in low-resource settings., Trial Registration: ClinicalTrials.gov NCT02656862., Competing Interests: The authors have declared that no competing interests exist.

Severe-febrile-illness (SFI) is a common cause of morbidity and mortality across sub-Saharan Africa (SSA). The burden of SFI in SSA is currently unknown and its estimation is fraught with challenges. This is due to a lack of diagnostic capacity for SFI in SSA, and thus a dearth of baseline data on the underlying etiology of SFI cases and scant SFI-specific causative-agent prevalence data. To highlight the public health significance of SFI in SSA, we developed a Bayesian model to quantify the incidence of SFI hospital admissions in SSA. Our estimates indicate a mean population-weighted SFI-inpatient-admission incidence rate of 18.4 (6.8-31.1, 68% CrI) per 1000 people for the year 2014, across all ages within areas of SSA with stable Plasmodium falciparum transmission. We further estimated a total of 16,200,337 (5,993,249-27,321,779, 68% CrI) SFI hospital admissions. This analysis reveals the significant burden of SFI in hospitals in SSA, but also highlights the paucity of pathogen-specific prevalence and incidence data for SFI in SSA. Future improvements in pathogen-specific diagnostics for causative agents of SFI will increase the abundance of SFI-specific prevalence and incidence data, aid future estimations of SFI burden, and enable clinicians to identify SFI-specific pathogens, administer appropriate treatment and management, and facilitate appropriate antibiotic use., Competing Interests: The authors have declared that no competing interests exist.

Background: China's 1-3-7 approach was extensively implemented to monitor the timeframe of case reporting, case investigation and foci response in the malaria elimination. However, activities before diagnosis and reporting (before '1') would counteract the efficiency of 1-3-7 approach but few data have evaluated this issue. This study aims to evaluate the timelines between onset of fever and diagnosis at healthcare facilities in Shanxi Province., Methods: Routine data were extracted from IDIRMS and NMISM database from 2013 to 2018. Time intervals between onset of fever and healthcare-seeking and between healthcare-seeking and diagnosis were calculated. Each of the documented malaria cases was geo-coded and paired to the county-level layers of polygon., Results: A total of 90 cases were reported in 2013-2018 in Shanxi Province, and 73% of cases reported at provincial health facilities. All malaria cases were imported from Africa (90%) and Southeast Asia (10%) especially around the Chinese Spring Festival (n = 46, 51%). The median days between fever and healthcare-seeking and between healthcare-seeking and diagnosis of malaria were 3 and 2, respectively., Conclusions: The current "1-3-7" approach is well executed in Shanxi Province, but delays intervals observed in case finding before 1-3-7 approach occurred in all levels of facilities in Shanxi Province, which imply that more efforts are highlighted for timely case finding. Health education should be provided for improving awareness of healthcare-seeking, and various technical training aiming at the physicians should be carried out to improve diagnosis of malaria.

Introduction: With the ability to diagnose malaria with rapid diagnostic tests (mRDT), interest in improving diagnostics for non-malarial fevers has increased. Understanding how health providers diagnose and treat fevers is important for identifying additional tools to improve outcomes and reduce unnecessary antibiotic prescribing, particularly in areas where access to laboratory diagnostics is limited. This study aimed to understand rural health providers' practice patterns, both quantitatively and qualitatively, and influences on diagnostic and treatment decision-making., Methods: A mixed-methods study was conducted in Mulanje and Phalombe districts in southern Malawi. Retrospective data on diagnoses and treatments of febrile illness from seven mobile clinic logbooks were collected for a 2-month period in both the dry and wet seasons. Mobile health clinics visited remote villages in southern Malawi once every 7 days. Records from all patients with a recorded axillary temperature of 37.5&ordm;C or higher or reported history of fever within 48 hours, and a negative mRDT, were included in the analysis. Key informant interviews were conducted with 31 mobile clinic health workers who triage, diagnose, and treat patients as well as dispense medication., Results: In total, 30 672 febrile patients were seen during the study period. Of those, 9924 (32%) tested negative for malaria by mRDT. Acute respiratory infection was the most common diagnosis for mRDT-negative patients (44.6%), and this number increased in the rainy season as compared to the dry season (odds ratio=2.18, 95% confidence interval=2.01-2.36). Over half (60%) of mRDT-negative patients received antibiotics as a treatment. Almost all the health providers in this study reported limited training in non-malarial fever management, despite the fact that roughly 30% of all patients with fever seen at the mobile clinics tested negative by mRDT. Without diagnostic tools beyond mRDTs, providers relied heavily on patient history to guide treatment decisions., Conclusion: Additional simple-to-use diagnostic tests as well as additional training in patient examination and clinical assessment are needed in rural settings where health providers risk over-prescribing antibiotics or missing a potentially dangerous infection in febrile patients who test negative for malaria.

Acute undifferentiated febrile illness (AUFI) has been a diagnostic dilemma in the tropics. Without accurate point-of-care tests, information on local pathogens and clinical parameters is essential for presumptive diagnosis. A prospective hospital-based study was conducted at the Bangkok Hospital for Tropical Diseases from 2013 to 2015 to determine common etiologies of AUFI. A total of 397 adult AUFI cases, excluding malaria by blood smear, were enrolled. Rapid diagnostic tests for tropical infections were performed on admission, and acute and convalescent samples were tested to confirm the diagnosis. Etiologies could be identified in 271 (68.3%) cases. Dengue was the most common cause, with 157 cases (39.6%), followed by murine typhus (20 cases; 5.0%), leptospirosis (16 cases; 4.0%), influenza (14 cases; 3.5%), and bacteremia (six cases; 1.5%). Concurrent infection by at least two pathogens was reported in 37 cases (9.3%). Furthermore, characteristics of dengue and bacterial infections (including leptospirosis and rickettsioses) were compared to facilitate dengue triage, initiate early antibiotic treatment, and minimize unnecessary use of antibiotics. In conclusion, dengue was the most common pathogen for AUFI in urban Thailand. However, murine typhus and leptospirosis were not uncommon. Empirical antibiotic treatment using doxycycline or azithromycin might be more appropriate, but cost-benefit studies are required. Physicians should recognize common causes of AUFI in their localities and use clinical and laboratory clues for provisional diagnosis to provide appropriate treatment while awaiting laboratory confirmation.

Malaria, arbovirus infection and travelers' diarrhea are among the most common etiologies of fever after a stay in the tropics. Because the initial symptoms of these diseases often overlap, the differential diagnostic remains a challenge. The aim of this study was to establish the effectiveness of platelet and leukocyte counts in the differential diagnosis of fever in the returning traveler. Between 2013 and 2016, patients with a clinical suspicion of malaria, who had thick blood smears performed were retrospectively included. The microbiological etiology of each episode was established based on molecular detection in the case of arbovirus infection, the detection of pathogens in stool samples for diarrhea and other gastrointestinal symptoms and the thick and thin blood smear results for malaria. A total of 1,218 episodes were included. Malaria, arbovirus infection, and diarrhea and other gastrointestinal symptoms caused 102 (8.4%), 68 (5.6%), and 72 (5.9%) episodes, respectively. The median platelet counts in malaria episodes were 89 × 10 9 /L and thrombocytopenia (< 150,000 × 10 9 platelets/L) yielded a 98% negative predictive value to predict malaria. The median leukocyte counts in arbovirus infection episodes were 3.19 × 10 9 /L and leucopenia (< 4 × 10 9 leukocytes/L) yielded a 97.9% negative predictive value to predict arbovirus infections. Platelet and leukocyte counts were not significantly altered in episodes caused by diarrhea and other gastrointestinal symptoms. Initial platelet and leukocyte counts might be useful for the clinical differential diagnosis of fever in the returning traveler. Although these results are insufficient to establish a diagnosis, they should be considered in the initial clinical assessment.

Objective: Rapid diagnostic tests have been of tremendous help in malaria control in endemic areas, helping in diagnosis and treatment of malaria cases. It is heavily relied upon in many endemic areas where microscopy cannot be obtained. However, caution should be taken in the interpretation of its result in clinical setting due to its limitations and inherent weakness. This paper seeks to present the varying malaria RDT test results, the possible interpretations and explanation of these results common in endemic regions. Published works on malaria RDT studies were identified using the following search terms "malaria RDT in endemic areas", "Plasmodium falciparum and bacterial coinfection" "Plasmodium falciparum RDT test results in children in endemic areas" in Google Scholar and PubMed., Results: The review results show that RDT positive results in febrile patients can either be true or false positive. True positive, representing either a possible single infection of Plasmodium or a co-infection of bacteria and P. falciparum. False RDT negative results can be seen in febrile patient with P. falciparum infection in prozone effect, Histidine rich protein 2 (HRP2) gene deletion and faulty RDT kits. Hence, a scale up of laboratory facilities especially expert microscopy and other diagnostic tools is imperative.

Background: In Nigeria, where malaria is endemic, greater than 70% of febrile illnesses are treated presumptively as malaria, often without a laboratory evaluation for other possible causes of fever. This cross-sectional study evaluated the presence of dengue virus infection in febrile patients, presumptively diagnosed of malaria infections in the clinic., Methodology: Blood samples were collected from 529 febrile patients (246 in Jos and 283 in Maiduguri) attending the general outpatient clinics of the Jos University Teaching Hospital (JUTH) and the University of Maiduguri Teaching Hospital (UMTH) and tested for anti-dengue immunoglobulin M (IgM) and immunoglobulin G (IgG), as well as anti-non-structural protein (NS1) by ELISA. The samples were also evaluated for presence of P. falciparum malaria parasites by microscopic examination of Giemsa-stained blood smears., Results: The prevalence of confirmed, highly suggestive and probable dengue virus infections categorized in relation to duration of illness since onset of fever were 2.3%, 5.5% and 1.5% respectively, while the prevalence of anti-flavivirus IgG and IgM seropositivity was 11.7%. In a total of 117 (22.1%) patients (32 in Jos, 85 in Maiduguri), malaria parasites were detected by blood smear microscopy, out of which 7 (6%) also had a positively confirmed, highly suggestive or probable dengue test result., Conclusion: Although the high cross-reactivity of anti-flavivirus antibodies should be taken into account in the interpretation of the seroprevalence data, our findings suggest a significant presence of dengue virus in this environment, some of which may otherwise be misdiagnosed as malaria. These findings are strong enough to recommend serological screening for anti-dengue virus titer and NS1 antigen for all febrile patients, as part of fever diagnostic protocols in tropical regions. Given the prevalence of dengue virus infections, there is also a need for a dengue control program and public education to prevent outbreaks and occurrence of severe dengue complications., (© 2018 The College of Medicine and the Medical Association of Malawi.)

Introduction: A routine diagnosis of Dengue virus (DENV) infection is not usually conducted in hospitals. Because symptoms overlap, many potential febrile illnesses due to DENV may be confused for malaria, typhoid or paratyphoid (enteric) fever. The absence of data on DENV exposure rates among children attending health facilities could undermine management of this disease. This study aimed to investigate the seroprevalence of dengue virus infection in children presenting febrile illness in some public health facilities in Cameroon., Methods: A cross-sectional study was performed in children ≤ 15 years attending seven urban and three semi-urban public hospitals of Cameroon. From each volunteer, 2ml of whole blood was collected and tested for dengue virus IgM, malaria (Pf/Pan antigens) and enteric fever (Typhoid IgM) using rapid diagnostic tests (RDT); in order to allow the healthcare workers to quickly put the positive cases under appropriate treatment. Positive cases of dengue virus infection were confirmed by indirect ELISA. Data analysis were performed using the statistical package for social sciences software, version 22.1., Results: A total of 961 children were enrolled in the study and 492 (51.2%) were infected with at least one of the three pathogens. Overall, DENV IgM seroprevalence among febrile children was 14.4% (138/961). About 390 (40.6%) and 22 (2.3%) had malaria (Pf/Pan Ag) and enteric fever (Typhoid IgM) respectively. Co-infection with dengue virus was found in 51 (5.3%) participants. The dengue virus IgM seroprevalence was higher in Bankim (19.3%), Ntui (18.3%) and Douala (18.2%)., Conclusion: Dengue virus infection seroprevalence appears to be low in children presenting with febrile illness in the studied health centres in Cameroon but call for more attention and research to further characterise the circulating strains of the dengue virus., Competing Interests: The authors declare no competing interests.

Background: There is limited information on uptake of malaria testing among migrants who are a 'high-risk' population for malaria. This was an explanatory mixed-methods study. The quantitative component (a cross sectional analytical study-nation-wide migrant malaria survey in 2016) assessed the knowledge; health-seeking; and testing within 24 h of fever and its associated factors. The qualitative component (descriptive design) explored the perspectives of migrants and health care providers [including village health volunteers (VHV)] into the barriers and suggested solutions to increase testing within 24 h. Quantitative data analysis was weighted for the three-stage sampling design of the survey. Qualitative data analysis involved manual descriptive thematic analysis., Results: A total of 3230 households were included in the survey. The mean knowledge score (maximum score 11) for malaria was 5.2 (0.95 CI 5.1, 5.3). The source of information about malaria was 80% from public health facility staff and 21% from VHV. Among 11 193 household members, 964 (8.6%) had fever in last 3 months. Health-seeking was appropriate for fever in 76% (0.95 CI 73, 79); however, only 7% (0.95 CI 5, 9) first visited a VHV while 19% (0.95 CI 16, 22) had self-medication. Of 964, 220 (23%, 0.95 CI 20, 26) underwent malaria blood testing within 24 h. Stable migrants, high knowledge score and appropriate health-seeking were associated with testing within 24 h. Qualitative findings showed that low testing within 24 h despite appropriate health-seeking was due to lack of awareness among migrants regarding diagnosis services offered by VHV, delayed health-seeking at public health facilities and not all cases of fever being tested by VHV and health staff. Providing appropriate behaviour change communication for migrants related to malaria, provider's acceptance for malaria testing for all fever cases and mobile peer volunteer under supervision were suggested to overcome above barriers., Conclusions: Providers were not testing all migrant patients with fever for malaria. Low uptake within 24 h was also due to poor utilization of services offered by VHV. The programme should seriously consider addressing these barriers and implementing the recommendations if Myanmar is to eliminate malaria by 2030.

Background: Malaria and acute bacterial meningitis (ABM) are the leading infectious causes of febrile encephalopathy in malaria endemic settings. The clinical distinction of the two conditions is complicated by overlap in clinical features., Objective: To determine the clinical predictors for malaria, ABM and treatment outcome in febrile children aged 2 months to 12 years with altered mentation at two tertiary hospitals in Northwestern Tanzania., Methods: Prospective study of 103 children to document demographic data and physical examination findings, such as level of consciousness and meningeal irritations. Laboratory results for cerebrospinal fluid, hemoglobin, malaria and HIV were also evaluated., Results: Age >60 months and hemoglobin ≤5 g/dl were independent predictors of malaria; (p = 0.013 and 0.004, respectively). HIV infection was the only predictor of meningitis, p = 0.037, and mortality was high if the diagnosis was unconfirmed., Conclusions: Children with febrile encephalopathy are more likely to have malaria than ABM if they have severe anemia.

Acute febrile illnesses (AFIs) in children from the developing world can have varying etiologies. Awareness of local epidemiology helps in prioritizing investigations and empiric treatment. This prospective study was carried out in a tertiary care center in North India, aiming to determine the burden, etiology, and outcome of AFI other than pneumonia and diarrhea in hospitalized children. A total of 613 consecutive children aged 3 months to 12 years with febrile illness of < 7 days during four selected months of 2014 representing different seasons were screened for eligibility. Those with acute respiratory diseases ( N = 175, 28.5%) and diarrheal illness ( N = 46, 7.5%) were excluded and 217 children were enrolled. Mean (standard deviation) age was 4.8 (3.4) years. Nearly half ( N = 91, 41.9%) presented in post-monsoon season. Diagnosis could be established in 187 (86.2%) children. Acute central nervous system infections were the most common ( N = 54, 24.8%). Among specific infections, scrub typhus was the most frequent ( N = 23, 10.5%) followed by malaria ( N = 14, 6.4%), typhoid ( N = 14, 6.5%), and viral hepatitis ( N = 13, 6.0%). Blood culture had a low (6.5%) yield; Salmonella typhi ( N = 6) and Staphylococcus aureus ( N = 5) were the common isolates. Serological tests were helpful in 50 (23%) cases. In multivariate analysis, hepatomegaly and/or splenomegaly independently predicted scrub typhus. Mortality rate was 10.1%. We conclude that AFI other than pneumonia and diarrhea are a significant burden and follow a seasonal trend. Scrub typhus has emerged as an important etiology of childhood AFIs in northern India. Periodic review of regional epidemiology will help in understanding the changing pattern of infectious diseases.

Universal malaria diagnostic testing of all fever cases is the first step in correct malaria case management. However, monitoring adherence to universal testing is complicated by unreliable recording and reporting of the true number of fever cases. We searched the literature to obtain gold-standard estimates for the proportion of patients attending outpatient clinics in sub-Saharan Africa with malarial and non-malarial febrile illness. To correct for differences in malaria transmission, we calculated the proportion of patients with fever after excluding confirmed malaria cases. Next, we analyzed routine data from Guinea and Senegal to calculate the proportion of outpatients tested after exclusion of confirmed malaria cases from the numerator and denominator. From 12 health facility surveys in sub-Saharan Africa with gold-standard fever screening, the median proportion of febrile illness among outpatients after exclusion of confirmed malaria fevers was 57% (range: 46-80%). Analysis of routine data after exclusion of confirmed malaria cases demonstrated much lower testing proportions of 23% (Guinea) and 13% (Senegal). There was substantial spatial and temporal heterogeneity in this testing proportion, and testing in Senegal was correlated with malaria season. Given the evidence from gold-standard surveys that at least 50% of non-malaria consultations in sub-Saharan Africa are for febrile illness, it appears that a substantial proportion of patients with fever are not tested for malaria in health facilities when considering routine data. Tracking the proportion of patients tested for malaria after exclusion of the confirmed malaria cases could allow programs to make inferences about malaria testing practices using routine data.

Background: The increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases., Methodology: Consenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status., Principal Findings: A total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections., Conclusions: These results raise questions about etiologies of fever in Malagasy communities. Nevertheless, we noted that viral infections and malaria still represent a significant proportion of causes of febrile illnesses. Interestingly our study allowed the detection of pathogens of public health interest such as Rift Valley Fever Virus but also the first case of laboratory-confirmed leptospirosis infection in Madagascar., Competing Interests: The authors have declared that no competing interests exist.

Objective: We assessed the prevalence of malarial fever and its association with demographic and socioeconomic factors in children <5 years of age., Methods: Using the data of Pakistan Demographic and Health Survey (PDHS), the socioeconomic condition (SEC) was assessed by using a household wealth index as a proxy indicator, generated through principal component analysis. Two-stage sampling was used for selection of households, and multilevel logistic regression analysis was performed., Results: The PDHS contains 10 935 children <5 years of age with valid information about malaria fever. In total, 36% (3930) children have malaria 2 weeks before the survey. A decreasing trend in prevalence of malaria fever was found with increasing SEC. Compared with SEC Quintile V, children of SEC Quintile I were more likely to get fever [adjusted odds ratio (AOR)=1.40 (1.15-1.69)] and of SEC Quintile II [AOR = 1.23 (1.03-1.45)]., Conclusion: SEC has a significant impact on the prevalence of malaria fever in the context of different regions in Pakistan.

Background: Monitoring the impact of case management strategies at large scale is essential to evaluate the public health benefit they confer. The use of methodologies relying on objective and standardized endpoints, such as drug levels in the blood, should be encouraged. Population drug use, diagnosis and treatment appropriateness in case of fever according to patient history and anti-malarials blood concentration was evaluated., Methods: A cross-sectional survey took place between May and August 2015 in three regions of Tanzania with different levels of malaria endemicity. Interviews were conducted and blood samples were collected by dried blood spots through household surveys for further anti-malarial measurements. Appropriate testing when individuals attended care was defined as a patient with history of fever being tested for malaria and appropriate treatment as (i) having anti-malarial in the blood if the test result was positive (ii) having anti-malarial in the blood if the person was not tested, and (iii) no anti-malarial in the blood when the test result was negative., Results: Amongst 6391 participants included in the anti-malarial analysis, 20.8% (1330/6391) had anti-malarial drug detected in the blood. Only 28.0% (372/1330) of the individuals with anti-malarials in their blood reported the use of anti-malarials within the previous month. Amongst all participants, 16.0% (1021/6391) reported having had a fever in the previous 2 weeks and 37.5% of them (383/1021) had detectable levels of anti-malarials in the blood. Of the individuals who sought care in health facilities, 69.4% (172/248) were tested and 52.0% (129/248) appropriately treated. When other providers were sought, 6% (23/382) of the persons were appropriately tested and 44.2% (169/382) appropriately treated. Overall, the proportion of individuals treated was larger than that being tested [47.3% (298/630) treated, 31.0% (195/630) tested]., Conclusion: This study showed high prevalence of circulating anti-malarial drug in the sampled population. Efforts should be made to increase rapid diagnostic tests use at all levels of health care and improve compliance to test result in order to target febrile patients that are sick with malaria and reduce drug pressure. Objective drug measurements collected at community level represent a reliable tool to evaluate overall impact of case management strategies on population drug pressure.

Background: This paper examines the impact of the scale-up of malaria rapid diagnostic tests (RDT) on routine clinical diagnosis procedures for febrile illness in primary healthcare settings in Papua New Guinea., Methods: Repeat, cross-sectional surveys in randomly selected primary healthcare services were conducted. Surveys included passive observation of consecutive febrile case management cases and were completed immediately prior to RDT scale-up (2011) and at 12- (2012) and 60-months (2016) post scale-up. The frequency with which specified diagnostic questions and procedures were observed to occur, with corresponding 95% CIs, was calculated for febrile patients prescribed anti-malarials pre- and post-RDT scale-up and between febrile patients who tested either negative or positive for malaria infection by RDT (post scale-up only)., Results: A total of 1809 observations from 120 health facilities were completed across the three survey periods of which 915 (51%) were prescribed an anti-malarial. The mean number of diagnostic questions and procedures asked or performed, leading to anti-malarial prescription, remained consistent pre- and post-RDT scale-up (range 7.4-7.7). However, alterations in diagnostic content were evident with the RDT replacing body temperature as the primary diagnostic procedure performed (observed in 5.3 and 84.4% of cases, respectively, in 2011 vs. 77.9 and 58.2% of cases in 2016). Verbal questioning, especially experience of fever, cough and duration of symptoms, remained the most common feature of a diagnostic examination leading to anti-malarial prescription irrespective of RDT use (observed in 96.1, 86.8 and 84.8% of cases, respectively, in 2011 vs. 97.5, 76.6 and 85.7% of cases in 2016). Diagnostic content did not vary substantially by RDT result., Conclusions: Rapid diagnostic tests scale-up has led to a reduction in body temperature measurement. Investigations are very limited when malaria infection is ruled out as a cause of febrile illness by RDT.

Objective: To analyze the working conditions and evaluate the effectiveness of blood smear examinations in fever patients after the start of national malaria elimination program (NMEP), and explore the suitable strategy for malaria diagnosis and surveillance in NMEP, so as to provide the evidence for the development and adaptation of malaria elimination strategies and measures in Jiangsu Province., Methods: The data of malaria epidemic situation reported by network, fever patients' blood test tables, and epidemiological surveys of malaria cases were collected and statistically analyzed by SPSS 16.0 in Jiangsu Province from 2010 to 2016., Results: A total of 2 367 cases of malaria cases were reported from 2010 to 2016. Among the 3 691 188 person-times of fever patients tested, there were 2 252 positives (0.06%). The number of blood tests of fever patients decreased from 742 900 in 2010 to 277 000 in 2016. At the same time, the positive rate increased from 0.04% in 2010 to 0.16% in 2016. The positive rate of blood tests of fever patients in 2016 was significantly higher than that in 2010 ( χ 2 = 161.61, P < 0.01). From 2010 to 2016 in Jiangsu province, the centers for disease control and prevention of cities and counties, that completed the blood review within 3 days, deleted 273 negative cases. In 2010, the centers for disease control and prevention of cities and counties deleted 61 negative cases, but in 2016, the centers deleted only 14 negative cases, and the negative rate of blood review in 2010 was significantly higher than that in 2016 ( χ 2 = 22.99, P < 0.01)., Conclusions: A large number of blood smear examinations have been tested in fever patients in Jiangsu Province. It not only conforms to the strong monitoring system requirements issued by World Health Organization (WHO) in malaria elimination, but also provides the evidence for no local malaria case in Jiangsu since 2012.

Background & Objectives: In India, certain geographic regions witness simultaneous outbreaks of two or more diseases like scrub typhus, dengue fever, malaria, leptospirosis and chikungunya during monsoon and post-monsoon period, sharing common indication of acute febrile illness. The objective of the present study was to assess the prevalence of coinfections among patients with acute undifferentiated fevers (AUF) admitted in a tertiary care hospital in the northern hilly state of Himachal Pradesh, India., Methods: This was a hospital based open cohort study conducted over a period of two months (September and October) in 2016. All the patients above the age of 18 yr admitted in medical wards and fulfilling the definition of AUF were included. The patients diagnosed with dual infections were the subjects of the study. Standard guidelines were used for case definitions of scrub typhus, dengue, chikungunya, malaria and leptospirosis., Results: Dual infections were noted in 16 patients admitted with AUF. The most common coinfection was scrub typhus and dengue, reported in 10 patients. Scrub typhus and leptospirosis coinfection was observed in three patients. Dengue and chikungunya was observed in one patient. Scrub typhus, dengue and vivax malaria was detected in one patient. Scrub typhus and vivax malaria was detected in one patient. Out of the 10 cases positive for both scrub and dengue, four had no history of travel outside Himachal Pradesh. All three cases positive for both scrub and leptospirosis were indigenous without any history of travel outside Kangra, Himachal Pradesh. The outcome of all the patients was with full recovery., Interpretation & Conclusion: The study established the presence of coinfections (mainly dengue fever and leptospirosis) as a cause of AUF in the study area, which is a nonendemic region. The role of easily available and widely performed serological tests in the aetiological diagnosis of AUF is significant. Studies are required to determine the normal titres in the local population before using the imported commercially available serological tests in the diagnosis of AUF., Competing Interests: None

Background: Private sector availability and use of malaria rapid diagnostic tests (RDTs) lags behind the public sector in Kenya. Increasing channels through which quality malaria diagnostic services are available can improve access to testing and help meet the target of universal diagnostic testing. Registered pharmacies are currently not permitted to perform blood tests, and evidence of whether malaria RDTs can be used by non-laboratory private providers in line with the national malaria control guidelines is required to inform ongoing policy discussions in Kenya., Methods: Two rounds of descriptive cross-sectional exit interviews and mystery client surveys were conducted at private health facilities and registered pharmacies in 2014 and 2015, 6 and 18 months into a multi-country project to prime the private sector market for the introduction of RDTs. Data were collected on reported RDT use, medicines received and prescribed, and case management of malaria test-negative mystery clients. Analysis compared outcomes at facilities and pharmacies independently for the two survey rounds., Results: Across two rounds, 534 and 633 clients (including patients) from 130 and 120 outlets were interviewed, and 214 and 250 mystery client visits were completed. Reported testing by any malaria diagnostic test was higher in private health facilities than registered pharmacies in both rounds (2014: 85.6% vs. 60.8%, p < 0.001; 2015: 85.3% vs. 56.3%, p < 0.001). In registered pharmacies, testing by RDT was 52.1% in 2014 and 56.3% in 2015. At least 75% of test-positive patients received artemisinin-based combination therapy (ACT) in both rounds, with no significant difference between outlet types in either round. Provision of any anti-malarial for test-negative patients ranged from 0 to 13.9% across outlet types and rounds. In 2015, mystery clients received the correct (negative) diagnosis and did not receive an anti-malarial in 75.5% of visits to private health facilities and in 78.4% of visits to registered pharmacies., Conclusions: Non-laboratory staff working in registered pharmacies in Kenya can follow national guidelines for diagnosis with RDTs when provided with the same level of training and supervision as private health facility staff. Performance and compliance to treatment recommendations are comparable to diagnostic testing outcomes recorded in private health facilities.

Millions of children travel annually, whether they are refugees, international adoptees, visitors, or vacationers. Although most young travelers do well, many develop a febrile illness during or shortly after their trips. Approaching a fever in the returning traveler requires an appropriate index of suspicion to diagnose and treat in a timely manner. As many as 34% of patients with recent travel history are diagnosed with routine infections, but serious infections such as malaria, enteric fever, and dengue fever should be on the differential diagnosis due the high morbidity and mortality in children., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare that we have no competing interests.

According to WHO recommendations, antimalarial drugs should be used only after a biological confirmation of a malaria attack. In order to better understand the diagnosis decision-making and the use of the malaria tests (immunochromatographic test RDT and direct microscope observation), a survey was carried out in two health facilities in the city of Cabinda, Angola in 2014. Diagnosis and drug prescriptions by the health staff were observed in 787 febrile children. It clearly appeared that there was a lack of trust of the health professionals in the test results, especially in the RDT. They tended to take into account test results irregularly, giving a diagnosis of malaria for half the febrile children despite only 16% of positive RDT. Acute febrile illness and malaria attacks seemed thus frequently confused. Alternative causes for fever were rarely sought out. Antimalarial drugs were hence overprescribed. Better training for staff and of their supervision by experimented practitioners are one of the means envisaged for triggering real change in the providers' practice., Competing Interests: The authors have no conflicts of interest to declare

Fevers of unknown origin complicate treatment and prevention of infectious diseases and are a global health burden. We examined risk factors of self-reported fever-categorized as "malarial" and "nonmalarial"-in households adjacent to national parks across the Ugandan Albertine Rift, a biodiversity and emerging infectious disease hotspot. Statistical models fitted to these data suggest that perceived nonmalarial fevers of unknown origin were associated with more frequent direct contact with wildlife and with increased distance from parks where wildlife habitat is limited to small forest fragments. Perceived malarial fevers were associated with close proximity to parks but were not associated with direct wildlife contact. Self-reported fevers of any kind were not associated with livestock ownership. These results suggest a hypothesis that nonmalarial fevers in this area are associated with wildlife contact, and further investigation of zoonoses from wildlife is warranted. More generally, our findings of land use-disease relationships aid in hypothesis development for future research in this social-ecological system where emerging infectious diseases specifically, and rural public health provisioning generally, are important issues.

Background: In this follow-up study, we aimed to establish the cut-off values of the volume, conductivity and scatter (VCS) parameters of leucocytes that significantly differ in dengue fever, malaria, scrub typhus and enteric fever, as described in our pilot study., Methods: A prospective observational case-control study was undertaken on patients with an established diagnosis of acute malaria (n=476), dengue fever (n=927), scrub typhus (n=425), bacterial sepsis (n=1598) or enteric fever (n=885) and the haematological and VCS data obtained by the Coulter LH 750 analyser were compared with controls., Results: Malaria significantly altered the platelet count and plateletcrit. The cut-offs for the monocyte volume, lymphocyte volume, neutrophil volume, neutrophil volume distribution width, lymphocyte volume distribution width, monocyte volume distribution width and neutrophil conductivity distribution width had 90% negative predictive values (NPVs) for malaria. Except for the proportion of monocytes, lymphocyte scatter distribution width and platelet distribution width, a >70% positive (PPV) and negative predictive value (NPV) for dengue was noted in all the haematological and VCS parameters analysed. While the cut-offs determined in scrub typhus had a good (>80%) PPV and NPV, a significant difference was seen in neutrophil, monocyte and lymphocyte conductivities, but with low sensitivity, specificity, PPV and NPV in enteric fever., Conclusions: Aetiology-specific changes occur both in numbers as well as in VCS properties in acute fevers. Formulae and/or algorithms need to be utilized to realize the full potential of the VCS technology.