Examining agreement between clinicians when assessing sick children.

BACKGROUND: Case management guidelines use a limited set of clinical features to guide assessment and treatment for common childhood diseases in poor countries. Using video records of clinical signs we assessed agreement among experts and assessed whether Kenyan health workers could identify signs defined by expert consensus. METHODOLOGY: 104 videos representing 11 clinical sign categories were presented to experts using a web questionnaire. Proportionate agreement and agreement beyond chance were calculated using kappa and the AC1 statistic. 31 videos were selected and presented to local health workers, 20 for which experts had demonstrated clear agreement and 11 for which experts could not demonstrate agreement. PRINCIPAL FINDINGS: Experts reached very high level of chance adjusted agreement for some videos while for a few videos no agreement beyond chance was found. Where experts agreed Kenyan hospital staff of all cadres recognised signs with high mean sensitivity and specificity (sensitivity: 0.897-0.975, specificity: 0.813-0.894); years of experience, gender and hospital had no influence on mean sensitivity or specificity. Local health workers did not agree on videos where experts had low or no agreement. Results of different agreement statistics for multiple observers, the AC1 and Fleiss' kappa, differ across the range of proportionate agreement. CONCLUSION: Videos provide a useful means to test agreement amongst geographically diverse groups of health workers. Kenyan health workers are in agreement with experts where clinical signs are clear-cut supporting the potential value of assessment and management guidelines. However, clinical signs are not always clear-cut. Video recordings offer one means to help standardise interpretation of clinical signs

Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya.

We have recently described 95 predicted alpha-helical coiled-coil peptides derived from putative Plasmodium falciparum erythrocytic stage proteins. Seventy peptides recognized with the highest level of prevalence by sera from three endemic areas were selected for further studies. In this study, we sequentially examined antibody responses to these synthetic peptides in two cohorts of children at risk of clinical malaria in Kilifi district in coastal Kenya, in order to characterize the level of peptide recognition by age, and the role of anti-peptide antibodies in protection from clinical malaria. Antibody levels from 268 children in the first cohort (Chonyi) were assayed against 70 peptides. Thirty-nine peptides were selected for further study in a second cohort (Junju). The rationale for the second cohort was to confirm those peptides identified as protective in the first cohort. The Junju cohort comprised of children aged 1-6 years old (inclusive). Children were actively followed up to identify episodes of febrile malaria in both cohorts. Of the 70 peptides examined, 32 showed significantly (p<0.05) increased antibody recognition in older children and 40 showed significantly increased antibody recognition in parasitaemic children. Ten peptides were associated with a significantly reduced odds ratio (OR) for an episode of clinical malaria in the first cohort of children and two of these peptides (LR146 and AS202.11) were associated with a significantly reduced OR in both cohorts. LR146 is derived from hypothetical protein PFB0145c in PlasmoDB. Previous work has identified this protein as a target of antibodies effective in antibody dependent cellular inhibition (ADCI). The current study substantiates further the potential of protein PFB0145c and also identifies protein PF11_0424 as another likely target of protective antibodies against P. falciparum malaria

Evaluating Different Dimensions of Programme Effectiveness for Private Medicine Retailer Malaria Control Interventions in Kenya

BACKGROUND: Private medicine retailers (PMRs) are key partners in the home management of fevers in many settings. Current evidence on effectiveness for PMR interventions at scale is limited. This study presents evaluation findings of two different programs implemented at moderate scale targeting PMRs for malaria control in the Kisii and Kwale districts of Kenya. Key components of this evaluation were measurement of program performance, including coverage, PMR knowledge, practices, and utilization based on spatial analysis. METHODOLOGY/PRINCIPAL FINDINGS: The study utilized mixed quantitative methods including retail audits and surrogate client surveys based on post-intervention cross-sectional surveys in intervention and control areas and mapping of intervention outlets. There was a large and significant impact on PMR knowledge and practices of the program in Kisii, with 60.5% of trained PMRs selling amodiaquine medicines in adequate doses compared to 2.8% of untrained ones (OR; 53.5: 95% CI 6.7, 428.3), a program coverage of 69.7% targeted outlets, and a potential utilization of about 30,000 children under five. The evaluation in Kwale also indicates a significant impact with 18.8% and 2.3% intervention and control PMRs selling amodiaquine with correct advice, respectively (OR; 9.4: 95% CI 1.1, 83.7), a program coverage of 25.3% targeted outlets, and a potential utilization of about 48,000 children under five. A provisional benchmark of 7.5 km was a reasonable threshold distance for households to access PMR services. CONCLUSIONS/SIGNIFICANCE: This evaluation show that PMR interventions operationalized in the district level settings are likely to impact PMR knowledge and practices and lead to increased coverage of appropriate treatment to target populations. There is value of evaluating different dimensions of public health programs, including quality, spatial access, and implementation practice. This approach strengthens the potential contribution of pragmatic study designs to evaluating public health programs in the real world

The Use of Mosquito Nets and the Prevalence of Plasmodium falciparum Infection in Rural South Central Somalia

BACKGROUND: There have been resurgent efforts in Africa to estimate the public health impact of malaria control interventions such as insecticide treated nets (ITNs) following substantial investments in scaling-up coverage in the last five years. Little is known, however, on the effectiveness of ITN in areas of Africa that support low transmission. This hinders the accurate estimation of impact of ITN use on disease burden and its cost-effectiveness in low transmission settings. METHODS AND PRINCIPAL FINDINGS: Using a stratified two-stage cluster sample design, four cross-sectional studies were undertaken between March-June 2007 across three livelihood groups in an area of low intensity malaria transmission in South Central Somalia. Information on bed net use; age; and sex of all participants were recorded. A finger prick blood sample was taken from participants to examine for parasitaemia. Mantel-Haenzel methods were used to measure the effect of net use on parasitaemia adjusting for livelihood; age; and sex. A total of 10,587 individuals of all ages were seen of which 10,359 provided full information. Overall net use and parasite prevalence were 12.4% and 15.7% respectively. Age-specific protective effectiveness (PE) of bed net ranged from 39% among <5 years to 72% among 5-14 years old. Overall PE of bed nets was 54% (95% confidence interval 44%-63%) after adjusting for livelihood; sex; and age. CONCLUSIONS AND SIGNIFICANCE: Bed nets confer high protection against parasite infection in South Central Somalia. In such areas where baseline transmission is low, however, the absolute reductions in parasitaemia due to wide-scale net use will be relatively small raising questions on the cost-effectiveness of covering millions of people living in such settings in Africa with nets. Further understanding of the progress of disease upon infection against the cost of averting its consequent burden in low transmission areas of Africa is therefore required

Should first-line empiric treatment strategies cover coagulase-negative staphylococcal infections in severely malnourished or HIV-infected children in Kenya?

BACKGROUND: Bloodstream infection is a common cause of morbidity in children aged andlt;5 years in developing countries. In studies reporting bacteremia in Africa, coagulase-negative Staphylococci (CoNS) are commonly isolated. However, it is currently unclear whether children who are highly susceptible to infection because of severe acute malnutrition (SAM) or HIV should be treated with antimicrobials specifically to cover CoNS. We aimed to determine the clinical significance of CoNS amongst children admitted to a rural hospital in Kenya in relation to nutritional and HIV status. METHODS: Systematically collected clinical and microbiological surveillance data from children aged 6-59 months admitted to Kilifi County Hospital (2007-2013) were analysed. Multivariable regression was used to test associations between CoNS isolation from blood cultures and SAM (MUAC andlt;11.5cm or nutritional oedema (kwashiorkor)), and HIV serostatus; and among children with SAM or HIV, associations between CoNS isolation and mortality, duration of hospitalization and clinical features. RESULTS: CoNS were isolated from blood culture in 906/13,315 (6.8%) children, of whom 135/906 (14.9%) had SAM and 54/906 (6.0%) were HIV antibody positive. CoNS isolation was not associated with SAM (MUACandlt;11.5cm (aOR 1.11, 95% CI 0.88-1.40) or kwashiorkor (aOR 0.84, 95% CI 0.48-1.49)), or a positive HIV antibody test (aOR 1.25, 95% CI 0.92-1.71). Among children with SAM or a positive HIV antibody test, CoNS isolation was not associated with mortality or prolonged hospitalization. CONCLUSION: In a large, systematic study, there was no evidence that antimicrobial therapy should specifically target CoNS amongst children with SAM or HIV-infection or exposure

Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage

<p>Abstract</p> <p>Background</p> <p>Hypoglycaemia is an independent risk factor for death in severe malaria and a recognized adverse treatment effect of parenteral quinine. In 2006 our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10 mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new WHO guidelines. This presented us with the opportunity to examine whether there was any dose relationship of quinine and hypoglycaemia occurrence.</p> <p>Methods</p> <p>Retrospective case notes review of all children admitted to hospital with severe falciparum malaria between April 2002 - July 2009, before and after the introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels were measured until intravenous quinine was discontinued. Clinical events immediately preceding or concurrent with each episode of hypoglycaemia (glucose < = 3.0 mmol/l) were recorded.</p> <p>Results</p> <p>954 children received the old quinine regime and 283 received the new regime. We found no evidence of an increased prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2 mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but less commonly with seizures (10%). Disruption of maintenance fluids and/or blood transfusion concurred with 42% of the hypoglycaemia episodes. Post admission hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P < 0.01.</p> <p>Conclusion</p> <p>There was no evidence to indicate a dose relationship between quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity features, disruption of glucose infusion and transfusion. Careful glucose monitoring should be targeted to these complications where resources are limited.</p

The Impact of Retail-Sector Delivery of Artemether–Lumefantrine on Malaria Treatment of Children under Five in Kenya: A Cluster Randomized Controlled Trial

In a cluster randomized trial, Beth Kangwana and colleagues find that provision of subsidized packs of the malaria therapy artemether-lumefantrine to shops more than doubled the proportion of children with fever who received drugs promptly

Changes in susceptibility to life-threatening infections after treatment for complicated severe malnutrition in Kenya

Background Goals of treating childhood Severe Acute Malnutrition (SAM), besides anthropometric recovery and preventing short-term mortality, include reducing risks of subsequent serious infections. How quickly and how much the risk of serious illness changes during rehabilitation is unknown, but could inform improving design and scope of interventions. Objective To investigate changes in the risk of life-threatening events (LTEs) in relation to anthropometric recovery from SAM. Design Secondary analysis of a clinical trial including 1,778 HIV-uninfected Kenyan children aged 2-59 months with complicated SAM, enrolled following the inpatient stabilization phase of treatment, and followed for 12 months. The main outcome was LTEs, defined as infections requiring re-hospitalization or causing death. We examined anthropometry measured at months one, three and six after enrolment in relation to LTEs occurring during the 6 months following each of these time points. Results During 12 months, there were 823 LTEs (257 fatal), predominantly severe pneumonia and diarrhea. At months one, three and six, 557(34%), 764(49%) and 842(56%) children had WHZ≥-2 respectively which, compared to WHZ Conclusion Anthropometric response was associated with rapid and substantial reduction risk of LTEs. However, reduction in susceptibility lagged behind anthropometric improvement. Disease events, alongside anthropometric assessment may provide a clearer picture of the effectiveness of interventions. Robust protocols for detecting and treating poor anthropometric recovery, and addressing broader vulnerabilities that complicated SAM indicates may save lives.</p

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded