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Streptococcus pneumoniae is the main bacterial pathogen causing respiratory infections. Since the COVID-19 pandemic emerged, less pneumococcal disease was identified by surveillance systems around the world. Measures to prevent transmission of SARS-CoV-2 also reduce transmission of pneumococci, but this would gradually lead to lower disease rates. Here, we explore additional factors that have contributed to the instant drop in pneumococcal disease cases captured in surveillance. Our observations on referral practices and other impediments to diagnostic testing indicate that residual IPD has likely occurred but remained undetected by conventional hospital-based surveillance. Depending on setting, we discuss alternative monitoring strategies that could improve sight on pneumococcal disease dynamics.

Background In low- and middle-income countries, surveillance of antimicrobial resistance (AMR) is mostly hospital-based and, in view of poor access to clinical microbiology, biased to more resistant pathogens. We aimed to assess AMR among Escherichia coli isolates obtained from urine cultures of pregnant women as an indicator for community AMR and compared the AMR results with those from E. coli isolates obtained from febrile patients in previously published clinical surveillance studies conducted within the same population in Nanoro, rural Burkina Faso. We furthermore explored feasibility of adding urine culture to standard antenatal care in a rural sub-Saharan African setting. Methods Between October 2016–September 2018, midstream urine samples collected as part of routine antenatal care in Nanoro district were cultured by a dipslide method and screened for antibiotic residues. Significant growth was defined as a pure culture of Enterobacterales at counts of ≥ 104 colony forming units/ml. Results Significant growth was observed in 202/5934 (3.4%) cultures; E. coli represented 155 (76.7%) of isolates. Among E. coli isolates, resistance rates to ampicillin, cotrimoxazole and ciprofloxacin were respectively 65.8%, 64.4% 16.2%, compared to 89.5%, 89.5% and 62.5% among E. coli from clinical isolates (n = 48 of which 45 from blood cultures). Proportions of extended spectrum beta-lactamase producers and multidrug resistance were 3.2% and 5.2% among E. coli isolates from urine in pregnant women versus 35.4%, and 60.4% respectively among clinical isolates. Conclusions The E. coli isolates obtained from healthy pregnant women had significantly lower AMR rates compared to clinical E. coli isolates, probably reflecting the lower antibiotic pressure in the pregnant women population. Adding urine culture to the routine urine analysis (dipstick) of antenatal care was feasible. The dipslide culture method was affordable and user-friendly and allowed on-site inoculation and easy transport; challenges were contamination (midstream urine sampling) and the semi-quantitative reading. Provided confirmation of the present findings in other settings, E. coli from urine samples in pregnant women may be a potential indicator for benchmarking, comparing, and monitoring community AMR rates across populations over different countries and regions.

BackgroundIn low- and middle-income countries, the prevalence of antimicrobial resistance (AMR) is increasing. To control AMR, WHO recommends monitoring antibiotic use, in particular Watch antibiotics. These are critically important antibiotics, with restricted use because at risk of becoming ineffective due to increasing AMR. We investigated pre-hospital antibiotic use in rural Burkina Faso.MethodsDuring 2016–2017, we collected data from patients aged > 3 months presenting with severe acute fever to the rural hospital of Nanoro Health District, Burkina Faso, including antibiotic use in the two weeks prior to consultation or hospitalization. We analysed reported antibiotic use by applying the WHO Access, Watch, Reserve classification.ResultsOf 920 febrile participants (63.0% ≤ 14 years), pre-hospital antibiotic use was reported by 363 (39.5%). Among these 363, microbiological diagnoses were available for 275 (75.8%) patients, of whom 162 (58.9%) were non-bacterial infections. Use of more than one antibiotic was reported by 58/363 (16.0%) participants. Of 491 self-referred patients who did not previously visit a primary health care center, 131 (26.7%) reported antibiotic use. Of 424 antibiotics reported, 265 (62.5%) were Access and 159 (37.5%) Watch antibiotics. Watch antibiotic use was more frequent among patients > 14 year olds (51.1%) compared to those 0–14 year old (30.7%,p p = 0.004). Most frequently reported Watch antibiotics were ceftriaxone (114, 71.7%) and ciprofloxacin (32, 20.1%).ConclusionThe reported frequent use of Watch group antibiotics among febrile patients prior to presentation to the hospital in rural Burkina Faso highlights the need to develop targeted interventions to improve antibiotic use in community settings as part of strengthening antibiotic stewardship in low- and middle-income countries. This should include facilitating referral, access to qualified prescribers and diagnostic tools in rural primary health care centers.Trial registrationClinicalTrials.gov identifier: NCT02669823. Registration date was February 1, 2016.

Background Nasopharyngeal colonisation with clinically relevant bacterial pathogens is a risk factor for severe infections, such as pneumonia and bacteraemia. In this study, we investigated the determinants of nasopharyngeal carriage in febrile patients in rural Burkina Faso. Methods From March 2016 to June 2017, we recruited 924 paediatric and adult patients presenting with fever, hypothermia or suspicion of severe infection to the Centre Medical avec Antenne Chirurgicale Saint Camille de Nanoro, Burkina Faso. We recorded a broad range of clinical data, collected nasopharyngeal swabs and tested them for the presence of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Klebsiella pneumoniae by quantitative polymerase chain reaction. Using logistic regression, we investigated the determinants of carriage and aimed to find correlations with clinical outcome. Results Nasopharyngeal colonisation with S. pneumoniae, H. influenzae and M. catarrhalis was highly prevalent and strongly dependent on age and season. Females were less likely to be colonised with S. pneumoniae (OR 0.71, p = 0.022, 95% CI 0.53–0.95) and M. catarrhalis (OR 0.73, p = 0.044, 95% CI 0.54–0.99) than males. Colonisation rates were highest in the age groups K. pneumoniae prevalence was low and not significantly correlated with age or season. For S. pneumoniae and H. influenzae, we found a positive association between nasopharyngeal carriage and clinical pneumonia [OR 1.75, p = 0.008, 95% CI 1.16–2.63 (S. pneumoniae) and OR 1.90, p = 0.004, 95% CI 1.23–2.92 (H. influenzae)]. S. aureus carriage was correlated with mortality (OR 4.01, p Conclusions Age, sex and season are important determinants of nasopharyngeal colonisation with S. pneumoniae, H. influenzae and M. catarrhalis in patients with fever in Burkina Faso. S. pneumoniae and H. influenzae carriage is associated with clinical pneumonia and S. aureus carriage is associated with mortality in patients with fever. These findings may help to understand the dynamics of colonisation and the associated transmission of these pathogens. Furthermore, understanding the determinants of nasopharyngeal colonisation and the association with disease could potentially improve the diagnosis of febrile patients.

IntroductionPatients with clinical malaria have an increased risk for bacterial bloodstream infections. We hypothesized that asymptomatic malaria parasitemia increases susceptibility for bacterial infections through an effect on the innate immune system. We measured circulating cytokine levels and ex-vivo cytokine production capacity in asymptomatic malaria and compared with controls.MethodsData were collected from asymptomatic participants ex-vivo stimulated with S. aureus, E. coli LPS and Salmonella Typhimurium; cytokine concentrations (TNF-α, IFN-γ, IL-1β, IL-6, IL-10) were measured on supernatants using ELISA.ResultsIncluded were children with clinical malaria (n=118), bacteremia (n=22), malaria and bacteremia co-infection (n=9), asymptomatic malaria (n=125), and asymptomatic controls (n=237). Children with either clinical or asymptomatic malaria had higher plasma cytokine concentrations than controls. Cytokine concentrations correlated positively with malaria parasite density with the strongest correlation for IL-10 in both asymptomatic (r=0.63) and clinical malaria (r=0.53). Patients with bacteremia had lower circulating IL-10, TNF-α and IFN-γ and higher IL-6 concentrations, compared to clinical malaria. Ex-vivo whole blood cytokine production to LPS and S. aureus was significantly lower in asymptomatic malaria compared to controls. Whole blood IFN-γ and IL-10 production in response to Salmonella was also lower in asymptomatic malaria.InterpretationIn children with asymptomatic malaria, cytokine responses upon ex-vivo bacterial stimulation are downregulated. Further studies are needed to explore if the suggested impaired innate immune response to bacterial pathogens also translates into impaired control of pathogens such as Salmonella spp.

Background New hemocytometric parameters can be used to differentiate causes of acute febrile illness (AFI). We evaluated a software algorithm–Infection Manager System (IMS)—which uses hemocytometric data generated by Sysmex hematology analyzers, for its accuracy to detect bacteremia in AFI patients with and without malaria in Burkina Faso. Secondary aims included comparing the accuracy of IMS with C-reactive protein (CRP) and procalcitonin (PCT). Methods In a prospective observational study, patients of ≥ three-month-old (range 3 months– 90 years) presenting with AFI were enrolled. IMS, blood culture and malaria diagnostics were done upon inclusion and additional diagnostics on clinical indication. CRP, PCT, viral multiplex PCR on nasopharyngeal swabs and bacterial- and malaria PCR were batch-tested retrospectively. Diagnostic classification was done retrospectively using all available data except IMS, CRP and PCT results. Findings A diagnosis was affirmed in 549/914 (60.1%) patients and included malaria (n = 191) bacteremia (n = 69), viral infections (n = 145), and malaria-bacteremia co-infections (n = 47). The overall sensitivity, specificity, and negative predictive value (NPV) of IMS for detection of bacteremia in patients of ≥ 5 years were 97.0% (95% CI: 89.8–99.6), 68.2% (95% CI: 55.6–79.1) and 95.7% (95% CI: 85.5–99.5) respectively, compared to 93.9% (95% CI: 85.2–98.3), 39.4% (95% CI: 27.6–52.2), and 86.7% (95% CI: 69.3–96.2) for CRP at ≥20mg/L. The sensitivity, specificity and NPV of PCT at 0.5 ng/ml were lower at respectively 72.7% (95% CI: 60.4–83.0), 50.0% (95% CI: 37.4–62.6) and 64.7% (95% CI: 50.1–77.6) The diagnostic accuracy of IMS was lower among malaria cases and patients, Author summary This study describes the diagnostic accuracy of the Infection Manager System (IMS), a novel diagnostic algorithm for febrile illnesses that is equipped on a routine hematology analyzer. The latest generation hematology analyzers allow better differentiation between leukocyte subsets and their phenotype. The IMS was created, using differences in immune cell subsets (their activation status for instance), to differentiate viral from bacterial etiologies of fever. Such a tool may guide clinicians in their decision the initiate or withhold antimicrobial therapy. The study was carried out among febrile patients aged 3 months and older in rural Burkina Faso, a sub-Saharan African setting where malaria is endemic. Standard microbiological techniques such as blood culture were used as a reference to assess the diagnostic accuracy of IMS. We then compared the diagnostic accuracy of the IMS with the marketed biomarkers C-reactive protein (CRP) and procalcitonin (PCT). Our study showed that the diagnostic performance of the IMS was similar to CRP and better than PCT to detect bacteremia in patients with and without malaria co-infection. Further studies are needed to see if the IMS can be safely used to guide initial antimicrobial treatment and help to reduce further spread of antimicrobial resistance.

OBJECTIVES: Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. METHODS: In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. RESULTS: A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. CONCLUSIONS: Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics. ispartof: CLINICAL MICROBIOLOGY AND INFECTION vol:27 issue:4 pages:590-596 ispartof: location:England status: published

Asymptomatic malaria infections may affect red blood cell (RBC) homeostasis. Reports indicate a role for chronic hemolysis and splenomegaly, however, the underlying processes are incompletely understood. New hematology analysers provide parameters for a more comprehensive analysis of RBC hemostasis. Complete blood counts were analysed in subjects from all age groups (n = 1118) living in a malaria hyperendemic area and cytokines and iron biomarkers were also measured. Subjects were divided into age groups ( Trial registration: Prospective diagnostic study: ClinicalTrials.gov identifier: NCT02669823. Explorative cross-sectional field study: ClinicalTrials.gov identifier: NCT03176719.

Background Non-typhoidal Salmonella (NTS) serotypes Typhimurium and Enteritidis are a major cause of bloodstream infections in children in sub-Saharan Africa but their reservoir is unknown. We compared pairs of NTS blood and stool isolates (with the same NTS serotype recovered in the same patient) for genetic similarity. Methods Between November 2013 and April 2017, hospital-admitted children (29 days to 14 years) with culture-confirmed NTS bloodstream infections were enrolled in a cross-sectional study at Kisantu Hospital, DR Congo. Stool cultures for Salmonella were performed on a subset of enrolled children, as well as on a control group of non-febrile hospital-admitted children. Pairs of blood and stool NTS isolates were assessed for genetic similarity by multiple-locus variable-number of tandem repeats (MLVA) and genomics analysis. Results A total of 299 children with NTS grown from blood cultures (Typhimurium 68.6%, Enteritidis 30.4%, other NTS 1.0%) had a stool sample processed; in 105 (35.1%) of them NTS was detected (Typhimurium 70.5%, Enteritidis 25.7%, other NTS 3.8%). A total of 87/105 (82.9%) pairs of blood and stool NTS isolates were observed (representing 29.1% of the 299 children). Among 1598 controls, the proportion of NTS stool excretion was 2.1% (p < 0.0001). MLVA types among paired isolates were identical in 82/87 (94.3%) pairs (27.4% of the 299 children; 61/66 (92.4%) in Typhimurium and 21/21 (100%) in Enteritidis pairs). Genomics analysis confirmed high genetic similarity within 41/43 (95.3%) pairs, showing a median SNP difference of 1 (range 0–77) and 1 (range 0–4) for Typhimurium and Enteritidis pairs respectively. Typhimurium and Enteritidis isolates belonged to sequence types ST313 lineage II and ST11 respectively. Conclusion Nearly 30% of children with NTS bloodstream infection showed stool excretion of an NTS isolate with high genetic similarity, adding to the evidence of humans as a potential reservoir for NTS., Author summary Non-typhoidal Salmonella (NTS) is an important cause of bloodstream infections in sub-Saharan Africa, but little is known about its reservoir and transmission. We assessed the possibility of a human reservoir by culturing stool samples from children with NTS found in their blood. Next, we compared the obtained blood and stool NTS isolates for genetic similarity. We found that a high proportion of children with NTS in their blood also had NTS in their stool (35.1%) when compared to a control group of children without suspicion of bloodstream infection (2.1%). We observed that Salmonella Typhimurium and Salmonella Enteritidis were the main serotypes isolated from blood and stool, and that their proportions were similar within the different populations. We found that 94.3% of the paired NTS blood and stool isolates (or 27.4% of children with NTS in their blood and a stool culture done) were genetically similar to each other. This observation adds to the evidence of a potential human reservoir for NTS.

Background Salmonella Typhimurium and Enteritidis are major causes of bloodstream infection in children in sub-Saharan Africa. This study assessed evidence for their zoonotic versus human reservoir. Methods Index patients were children with blood culture confirmed Salmonella infection recruited during a microbiological surveillance study in Nanoro, rural Burkina between May 2013 and August 2014. After consent, their households were visited. Stool from household members and livestock (pooled samples per species) as well as drinking water were cultured for Salmonella. Isolates with identical serotype obtained from index patient and any household sample were defined as “paired isolates” and assessed for genetic relatedness by multilocus variable number tandem-repeat analysis (MLVA) and whole-genome sequencing (WGS). Results Twenty-nine households were visited for 32/42 (76.2%) eligible index patients: two households comprised two index patients each, and in a third household the index patient had a recurrent infection. Among the 32 index patients, serotypes were Salmonella Typhimurium (n = 26), Salmonella Enteritidis (n = 5) and Salmonella Freetown (n = 1). All Typhimurium isolates were sequence type (ST)313. Median delay between blood culture sampling and household visits was 13 days (range 6–26). Salmonella was obtained from 16/186 (8.6%) livestock samples (13 serotypes) and 18/290 (6.2%) household members (9 serotypes). None of the water samples yielded Salmonella. Paired Salmonella Typhimurium isolates were obtained from three households representing four index patients. MLVA types were identical in two pairs and similar in the third (consisting of two index patients and one household member). WGS showed a strong genetic relatedness with 0 to 2 core genome SNPs difference between pairs on a household level. Livestock samples did not yield any Salmonella Typhimurium or Salmonella Enteritidis, and the latter was exclusively obtained from blood culture. Other serotypes shared by human and/or livestock carriers in the same household were Salmonella Derby, Drac, Tennessee and Muenster. Conclusions/Significance The current study provides further evidence of a human reservoir for invasive non-Typhoidal Salmonella (iNTS) in sub-Saharan Africa., Author summary Non-Typhoidal Salmonella—particularly Salmonella Typhimurium sequence type (ST) 313—are among the most common causes of bloodstream infection in children in sub-Saharan Africa. To assess transmission and reservoir of this invasive serotype we performed a blood culture surveillance study among children < 15 years (index patients) in Nanoro, rural Burkina Faso. In case of blood culture confirmed invasive Non-Typhoidal Salmonella (iNTS) infection among index patients a household survey was performed, during which stool samples from household members, stool samples from livestock and water samples were obtained and cultured for Salmonella. Salmonella isolates obtained from blood culture of index patients were compared for genetic relatedness with Salmonella isolates obtained from samples taken from their corresponding household. In three households we found Salmonella Typhimurium ST 313 among both index patient and the stool sample of a household member, we found a strong genetic relatedness within each pair. There were no matching serotypes between index patients and livestock samples or water samples within households. Clusters from other serotypes were restricted to stool samples from household members and different species of livestock. Our results support the theory that iNTS has a human reservoir.

Campylobacter infection is a common cause of diarrhea among international travelers. We studied antibiotic resistance patterns among Campylobacter isolates obtained from international travelers according to travel destination. Three collections of isolates obtained from international travelers between 2007 and 2014 (Institute of Tropical Medicine, the “Laboratoire Hospitalier Universitaire de Bruxelles “and the Belgian National Reference Centre for Campylobacter) were used. Isolates were tested for minimal inhibitory concentration (MIC) values (E-test macromethod) for fluoroquinolones, macrolides, tetracyclines, amoxicillin–clavulanic acid, and meropenem. Single isolates from 261 travelers were available; median (IQR) age was 25.4 (4–42) years, 85.8% were symptomatic (information for 224 patients available). Overall resistance to ciprofloxacin was 60.9%, ranging from 50.8% in Africa to 75.0% in Asia. Resistance to erythromycin was 4.6%, with the highest rate observed for Southern Asia (15.2%, seven isolates, six of them recovered from patients returning from India). A total of 126 isolates (48.3%) were resistant to tetracycline. No resistance to amoxicillin–clavulanic acid or meropenem was detected. Ciprofloxacin resistance tended to increase over time (53.9% in 2007 versus 72.2% in 2014), erythromycin resistance remained stable (median annual resistance 4.2%). Most (86.2%) ciprofloxacin-resistant isolates had MIC values ≥32 mg/l, and all erythromycin-resistant isolates had MIC values ≥256 mg/l. Co-resistance to ciprofloxacin and erythromycin was observed in 11 (4.2%) isolates, seven of which came from Southern Asia. Among all regions of travel, more than half of Campylobacter isolates were resistant to ciprofloxacin. Overall resistance to erythromycin was below 5% but reached 15.2% in Southern Asia., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND This study reports the microbiological landscape of Salmonella Typhi and invasive nontyphoidal Salmonella (iNTS) in the Democratic Republic of the Congo (DRC). METHODS Blood cultures obtained from hospital-admitted patients suspected of bloodstream infection (BSI) in 4 of 11 provinces in DRC (Kinshasa, Bas-Congo, Equateur, and Orientale) were processed. Sampling had started in 2007; the results for the period 2011-2014 are reported. RESULTS Salmonella Typhi and iNTS were cultured from 194 (1.4%) and 840 (5.9%), respectively, of 14,110 BSI episodes and ranked first among BSI pathogens in adults (65/300 [21.7%]) and children (783/1901 [41.2%]), respectively. A total of 948 of 1034 (91.7%) isolates were available for analysis (164 Salmonella Typhi and 784 iNTS). Salmonella Typhimurium and Salmonella Enteritidis represented 386 (49.2%) and 391 (49.9%), respectively, of iNTS isolates, fluctuating over time and geography and increasing during the rainy season. Adults accounted for

Background Bloodstream infections (BSI) caused by Salmonella Typhi and invasive non-Typhoidal Salmonella (iNTS) frequently affect children living in rural sub-Saharan Africa but data about incidence and serotype distribution are rare. Objective The present study assessed the population-based incidence of Salmonella BSI and severe malaria in a Health and Demographic Surveillance System in a rural area with seasonal malaria transmission in Nanoro, Burkina Faso. Methods Children between 2 months—15 years old with severe febrile illness were enrolled during a one-year surveillance period (May 2013—May 2014). Thick blood films and blood cultures were sampled and processed upon admission. Population-based incidences were corrected for non-referral, health seeking behavior, non-inclusion and blood culture sensitivity. Adjusted incidence rates were expressed per 100,000 person-years of observations (PYO). Results Among children < 5 years old, incidence rates for iNTS, Salmonella Typhi and severe malaria per 100,000 PYO were 4,138 (95% Confidence Interval (CI): 3,740–4,572), 224 (95% CI: 138–340) and 2,866 (95% CI: 2,538–3,233) respectively. Among those aged 5–15 years, corresponding incidence rates were 25 (95% CI: 8–60), 273 (95% CI: 203–355) and 135 (95% CI: 87–195) respectively. Most iNTS occurred during the peak of the rainy season and in parallel with the increase of Plasmodium falciparum malaria; for Salmonella Typhi no clear seasonal pattern was observed. Salmonella Typhi and iNTS accounted for 13.3% and 55.8% of all 118 BSI episodes; 71.6% of iNTS (48/67) isolates were Salmonella enterica serovar Typhimurium and 25.4% (17/67) Salmonella enterica serovar Enteritidis; there was no apparent geographical clustering. Conclusion The present findings from rural West-Africa confirm high incidences of Salmonella Typhi and iNTS, the latter with a seasonal and Plasmodium falciparum-related pattern. It urges prioritization of the development and implementation of Salmonella Typhi as well as iNTS vaccines in this setting.