Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries.

BACKGROUND: Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens. METHOD: A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated. RESULTS: The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidal Salmonella, Plasmodium species and Mycobacterium tuberculosis as the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients. CONCLUSION: This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, combining available prevalence data with expert input, can result in a broadly applicable priority list. This comprehensive utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.

Community outbreak of cutaneous leishmaniasis in La Ribera region of Valencia, Spain: Public Health measures. / Brote comunitario de leishmaniasis cutánea en la comarca de La Ribera: a propósito de las medidas de Salud Pública.

INTRODUCTION: Outbreaks of human leishmaniasis are not very common in Spain, despite being considered an endemic disease. In this study, a new outbreak in the Valencian Community is presented. Its principal objective is to describe the clinical-epidemiological characteristics and to present the main Public Health measures established to contain the outbreak. METHODS: A case was defined as anyone residing in the village of Tous (in Valencian Community), diagnosed with leishmaniasis according to clinical and laboratory criteria, defined by the Epidemiological Surveillance Network, and date of symptoms onset between 1 January 2012 and 31 December 2013. A descriptive analysis was performed on the epidemiological variables collected. RESULTS: A total of 19 cases were reported from the 28th week of 2012 to the 30th week of 2013. Adults were most affected by the disease (73%). The most common clinical form was cutaneous leishmaniasis (89%). More than three-quarters (79%) of cases were confirmed by PCR. Species typing was performed on seven samples, with the parasite Leishmania infantum being identified. Patient outcome was favourable after physical (31%), or pharmacological (69%) treatment. Some kind of residual damage was observed in 37% of cases. Different measures were applied, aimed at health professionals, and vector and reservoir control, as well as general recommendations to the population for the containment of the outbreak. CONCLUSIONS: This cutaneous leishmaniasis outbreak confirms the endemic nature and the high prevalence of the disease in the Mediterranean area. The most commonly used treatment was intralesional meglumine antimoniate. A comprehensive plan of action had to be developed in order to control the outbreak.

Community deworming alleviates geohelminth-induced immune hyporesponsiveness.

In cross-sectional studies, chronic helminth infections have been associated with immunological hyporesponsiveness that can affect responses to unrelated antigens. To study the immunological effects of deworming, we conducted a cluster-randomized, double-blind, placebo-controlled trial in Indonesia and assigned 954 households to receive albendazole or placebo once every 3 mo for 2 y. Helminth-specific and nonspecific whole-blood cytokine responses were assessed in 1,059 subjects of all ages, whereas phenotyping of regulatory molecules was undertaken in 121 school-aged children. All measurements were performed before and at 9 and 21 mo after initiation of treatment. Anthelmintic treatment resulted in significant increases in proinflammatory cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) and mitogen, with the largest effect on TNF responses to PfRBCs at 9 mo-estimate [95% confidence interval], 0.37 [0.21-0.53], P value over time (Ptime) < 0.0001. Although the frequency of regulatory T cells did not change after treatment, there was a significant decline in the expression of the inhibitory molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on CD4+ T cells of albendazole-treated individuals, -0.060 [-0.107 to -0.013] and -0.057 [-0.105 to -0.008] at 9 and 21 mo, respectively; Ptime = 0.017. This trial shows the capacity of helminths to up-regulate inhibitory molecules and to suppress proinflammatory immune responses in humans. This could help to explain the inferior immunological responses to vaccines and lower prevalence of inflammatory diseases in low- compared with high-income countries.

Community-acquired diarrhea among children and adults in urban settings in Senegal: clinical, epidemiological and microbiological aspects.

BACKGROUND: Only limited data are available relating to the etiology of diarrhea in children and adults in Senegal. The aim of this prospective study was to describe the epidemiology and etiology of community-acquired diarrheal infections in children and adults living in urban settings. METHODS: A prospective study was carried out from March 2009 to December 2010, in the urban region of Dakar, Senegal. Patients with acute diarrhea were enrolled, interviewed to collect their clinical history, and their stools were tested for bacteria, virus and parasites. RESULTS: A total of 223 patients (including 112 children younger than five years old) with diarrhea were included. At least one enteropathogen was detected in 81% (180/223) of the patients: 29% (64/223) had bacterial infections (mainly diarrheagenic E. coli and Shigella spp), 21% (39/185) viral infections (mainly rotavirus) and 14% (31/223) parasitic infections. Co-infection was identified in 17.8% (32/180) of the patients. Viral infection was significantly more frequent in children under five years old during the dry season. Bacteria and parasites were equally frequent in all age groups. There was a seasonal variation of bacterial infections during the study period, with a higher proportion of infections being bacterial, and due to Salmonella spp. in particular, during the rainy season. CONCLUSION: Our study suggests that in urban settings in Senegal, rotavirus is the principal cause of pediatric diarrhea during the dry season and that the proportion of bacterial infections seems to be higher during the rainy season. Further work is needed to document the burden of diarrheal diseases in sub-Saharan urban communities and to identify risk factors, including those linked to the rapid and unplanned urbanization in Africa.

[Case report: Löffler's syndrome due to Ascaris lumbricoides mimicking acute bacterial community--acquired pneumonia]. / Olgu sunumu: akut bakteriyel toplum kökenli pnömoni klinigini taklit eden Ascaris lumbricoides'e bagli bir Löffler's sendromu.

In this study we present a patient with Loeffler's syndrome caused by Ascaris lumbricoides who presented with the clinical findings of community-acquired pneumonia (CAP). Our patient, who was twenty-five years old, and who had had symptoms such as coughing, expectorating, dyspnea and fever for approximately ten days, was hospitalized. We auscultated polyphonic rhonchuses at the both hemithoraxes. A chest X-ray revealed bilateral lower zone patch consolidation. Acute bacterial community acquired pneumonia (CAP) was diagnosed due to these findings and empirical antibiotic treatment was begun. Repeated sputum Gram stains were negative, and both sputum and blood cultures were sterile. A sputum smear was negative for acid-fast bacilli. The patient's fever and respiratory complaint did not respond to the empirical antibiotics therapy. During the course of advanced investigations, we measured peripheric eosinophilia, and high levels of total Eo and total IgE, and observed Ascaris lumbricoides eggs during stool examination. The patient was given a diagnosis of Loeffler's syndrome. Thereupon the patient was treated successfully with one dose of albendazol 400 mg. In conclusion, we suggest that Loeffler's syndrome must be considered early in the differential diagnosis for CAP when peripheric eosinophilia is seen in patients if they live in an endemic area for parasitic disease.

Structured surveillance of infectious intestinal disease in pre-school children in the community: 'The Nappy Study'.

The incidence and causes of infectious intestinal disease (IID) in children aged <5 years presenting to general practitioners (GPs) were estimated. During a 12-month period, soiled nappies were collected from children presenting with symptoms suggestive of IID in a network of 65 GPs located across England. Molecular methods were used to detect a range of enteric pathogens including viruses, bacteria and parasites. Genotyping was performed on rotavirus and norovirus isolates. A total of 583 nappies were collected from 554 children; a pathogen was detected in 361 (62%) specimens. In the 43 practices 1584 new episodes of IID were recorded in a population averaging 19774; the specimen capture rate was 28%. IID incidence peaked during March and April. Norovirus (24.5%), rotavirus (19.0%) and sapovirus (12.7%) were most commonly detected, and mixed infections were detected in 11.7% of cases. Strain characterization revealed G1P[8] (65.8%), G4P[4] (8.1%) and G9P[8] (8.1%) as the most common rotavirus genotypes, similar to the UK national distribution. GII-3 (42.9%) and GII-4 (39.7%) were the most common norovirus genotypes; this was significantly different (P<0.005) to the national distribution.

Prevalence of Taenia solium cysticercosis in swine from a community-based study in 21 villages of the Eastern Cape Province, South Africa.

The pork tapeworm, Taenia solium, causative organism of porcine cysticercosis and human neurocysticercosis is known to occur in areas of South Africa including Eastern Cape Province but, despite increasing reports of its occurrence throughout the subregion, the prevalence is yet to be clearly established. The parasite presents a potentially serious agricultural problem and public health risk in endemic areas. The human populations considered to be at highest risk of infection with this zoonotic helminth are people living in rural areas most of whom earn their livelihood wholly or partially through livestock rearing. Here we report on initial results of a community-based study of pigs owned by resource-poor, emerging pig producers from 21 villages in the Eastern Cape Province. Lingual examination (tongue palpation) in live pigs, two enzyme-linked immunosorbent assays (ELISAs), which detect parasite antigen (B158/B60 Ag-ELISA and HP10 Ag-ELISA) and an enzyme immunotransfer blot (EITB) assay, which detects antiparasite antibody, were used to verify endemicity and estimate apparent prevalence. In the absence of a gold standard true prevalence was obtained, using a Bayesian approach, with a model that uses both available data and prior information. Results indicate that the parasite is indeed present in the study villages and that true prevalence was 64.6%. The apparent prevalences as measured by each of the four tests were: 11.9% for lingual examination, 54.8% for B158/B60 Ag-ELISA, 40.6% for HP10 Ag-ELISA and 33.3% for EITB. This base-line knowledge of the prevalence of T. solium in pigs provides information essential to the design and monitoring of sustainable and appropriate interventions for cysticercosis prevention and control.

Legionella-like and other amoebal pathogens as agents of community-acquired pneumonia.

We tested serum specimens from three groups of patients with pneumonia by indirect immunofluorescence against Legionella-like amoebal pathogens (LLAPs) 1-7, 9, 10, 12, 13; Parachlamydia acanthamoeba strains BN 9 and Hall's coccus; and Afipia felis. We found that LLAPs play a role (albeit an infrequent one) in community-acquired pneumonia, usually as a co-pathogen but sometimes as the sole identified pathogen.

Prevalence of enteric pathogens among community based asymptomatic individuals.

BACKGROUND AND AIMS: The objective of this study was to describe the prevalence of pathogenic microorganisms in asymptomatic individuals in a community study in Melbourne, Australia. METHODS: The study population was a subset of 2803 individuals participating in the Water Quality Study; a community based randomized trial. Faecal specimens (1091) were collected over a 3-month period from asymptomatic individuals. Specimens were tested for a range of bacteria including Salmonella, Shigella and Campylobacter species. Rotavirus and adenovirus were detected using a Rota-Adeno latex kit, and protozoa were detected using a permanent stain (modified iron-haemotoxylin). RESULTS: Twenty-eight known pathogens were identified from the 1091 faecal specimens, a total carriage rate of 2.6%. Giardia species were present in 18 specimens (1.6%), Salmonella in four (0.4%), Campylobacter in one (0.1%), Cryptosporidium in four (0.4%) and adenovirus in one (0.1%). Blastocystis hominis was found in 65 specimens. The median age of those without a pathogen was 12.5 years compared with 6.6 years for those with a pathogen (P=0.02). CONCLUSIONS: Except for Giardia, pathogens were rarely found in asymptomatic individuals in the community. The prevalence of pathogens was higher in children than adults.

Study of Cyclospora cayetanensis in health care facilities, sewage water and green leafy vegetables in Nepal.

Cyclospora cayetanensis, a newly emerging parasite, is endemic in Nepal. A total of 2,123 stool specimens were collected from 3 health care facilities based on clinical symptoms during the period between 1995 to October, 1998. Out of these specimens, cayetanensis oocysts were found in 632 (29.8%). To identify possible sources for Cyclospora infection, drinking water, sewage water, green-leafy vegetables including fecal samples of various animals were collected and examined. The vegetable leaves were washed in distilled water then the washings, sewage water and drinking water were centrifuged and the sediment were examined microscopically. As a result, oocyst of Cyclospora were identified in sewage water and vegetable washings on four different occasions in June, August, October and November. The positive results were also confirmed as C. cayetanensis by development of 2 sporocysts after 2 week incubation period in potassium dichromate. A survey of 196 domestic animals from the same areas demonstrated that two chickens were positive for Cyclospora-like organism and others were negative. Although further studies are needed to clarify the direct link between Cyclospora infection and these sources, the results suggest that sewage water, green leafy vegetables are possible sources of infection and chickens could be possible reservoir host of Cyclospora in Nepal.

Cyclospora species as a gastrointestinal pathogen in immunocompetent hosts.

Previous reports of diarrhea resulting from Cyclospora species have been linked to travelers and immunocompromised patients. We conducted a prospective study of 1,042 formalin-ethyl acetate fecal concentrates collected from patients with diarrhea. Between May and November 1993, we identified three patients for whom studies were positive for nonrefractile spherical organisms measuring 10 microns in diameter and containing a cluster of refractile membrane-bound globules. The cysts exhibited variable acid fastness consistent with Cyclospora species. These three patients had no history of recent travel and presented with relapsing, watery, nonbloody diarrhea that lasted from 12 days to 8 weeks. No other parasitic or bacterial pathogens were identified in their stools. All three instances of diarrhea occurred in May or June. No common source of food or water was identified. None of these patients were immunosuppressed, and their diarrhea resolved spontaneously. We suggest that Cyclospora species should be considered in community-acquired diarrhea.

Distribution patterns of Tunga penetrans within a community in Trinidad, West Indies

This paper describes patterns of infection with Tunga penetrans within the town of Icacos, Trinidad, West Indies, assessed by the number of persons infected and the extent of the chigoe flea burden by physical examination. The overall prevalence of infection was 31.4 percent (102 infected persons) of the 325 persons examined (41 percent of males and 23 percent of females). Both measure showed a significant difference among the different age groups with a peak chigoe burden found in the 5-9, 10-14 and >55 age-groups with 9, 5.6 and 12 fleas per infected person respectively. The aggregated distribution of chigoe flea burden showed a few persons with many fleas and many persons with none (68 percent). In contrast, in chigoe flea burden there were no significant sex differences but age-associated differences (G=17.9; d.f. 7; P<0.01). It is recommended that all cases of tungiasis should be treated and the source of infection effectively managed or eradicated (AU)