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Abstract Background Primaquine is an important gametocytocidal drug that is combined with conventional malaria treatment for prevention of Plasmodium falciparum malaria transmission. Primaquine has been administered together on the first or the last day of conventional treatment but the impact of primaquine timing has never been examined. This study aimed to assess safety, efficacy and optimal timing of single full-dose (0.75 mg/kg) primaquine when added to a standard 6-dose regimen of artemether–lumefantrine (AL). Methods In an individual-level randomized controlled trial, enrolled participants who were G6PD normal and had uncomplicated P. falciparum malaria were randomly assigned to receive: AL only; AL and a single 0.75 mg/kg primaquine dose on the first day of AL (day 1); or AL and single 0.75 mg//kg primaquine on the last day of AL (day 3). On days 2, 3, 4, 8, 11 and 15, gametocytes were assessed and quantified by microscope and quantitative nuclear acid sequence based quantification (QT-NASBA). Results Overall, 111 participants aged between 3 and 17 years were randomly allocated to receive AL only (36) or combined with primaquine on day 1 (38), or primaquine on day 3 (37). Day 4 gametocyte prevalence in AL + day 1 primaquine was half the level seen in either AL + day 3 primaquine or AL only arm (11% [4/35] vs 26% [8/31] and 27% [8/30], respectively) albeit not statistically significant. A similar trend of lower gametocyte in the AL + day 1 primaquine verses AL + day 3 primaquine or AL only arm was observed in mean gametocyte density. Mean (sd) haemoglobin level in AL + day 3 primaquine arm recovered from -0.42(1.2) g/dl on day 2 to 0.35 (1.5) g/dl on day 15 of follow up. This was not the case in AL only and AL + day 1 primaquine arms during the same follow-up period, although the difference was not statistically significant (p = 318). No serious adverse events reported in the study. Across arms, 23% (26/111) of participants reported a total of 31 mild adverse events and the difference was not statistically significant (p = 0.477). Conclusion Primaquine administration on the first day of AL is well tolerated and as safe as later administration. Whilst the World Health Organization currently recommends a lower dose of primaquine (0.25 mg/kg), the findings are supportive of early primaquine administration when combined with artemisinin-combination therapy. ClinicalTrials.gov Registration NCT01906788…

Abstract Background The drug combination atovaquone–proguanil, is recommended for treatment of uncomplicated falciparum malaria in France. Despite high efficacy, atovaquone–proguanil treatment failures have been reported. Resistance to cycloguanil, the active metabolite of proguanil, is conferred by multiple mutations in the Plasmodium falciparum dihydrofolate reductase (pfdhfr) and resistance to atovaquone by single mutation on codon 268 of the cytochrome b gene (pfcytb). Case presentation A 47-year-old female, native from Congo and resident in France, was admitted in hospital for uncomplicated falciparum malaria with parasitaemia of 0.5%, after travelling in Congo (Brazzaville and Pointe Noire). She was treated with atovaquone–proguanil (250 mg/100 mg) 4 tablets daily for 3 consecutive days. On day 5 after admission she was released home. However, many weeks after this episode, without having left France, she again experienced fever and intense weakness. On day 39 after the beginning of treatment, she consulted for fever, arthralgia, myalgia, photophobia, and blurred vision. She was hospitalized for uncomplicated falciparum malaria with a parasitaemia of 0.375% and treated effectively by piperaquine–artenimol (320 mg/40 mg) 3 tablets daily for 3 consecutive days. Resistance to atovaquone–proguanil was suspected. The Y268C mutation was detected in all of the isolates tested (D39, D42, D47). The genotyping of the pfdhfr gene showed a triple mutation (N51I, C59R, S108N) involved in cycloguanil resistance. Conclusion This is the first observation of a late clinical failure of atovaquone–proguanil treatment of P. falciparum uncomplicated malaria associated with pfcytb 268 mutation in a traveller returning from Congo. These data confirm that the Y268C mutation is associated with delayed recrudescence 4 weeks or more after initial treatment. Although atovaquone–proguanil treatment failures remain rare, an increased surveillance is required. It is essential to declare and publish all well-documented cases of treatment failures because it is the only way to evaluate the level of resistance to atovaquone.…

Abstract Background Quality control of indoor residual spraying (IRS) is necessary to ensure that spray operators (SOs) deposit the correct concentration of insecticide on sprayed structures, while also confirming that spray records are not being falsified. Methods Using high-performance liquid chromatography (HPLC), this study conducted quality control of the organophosphate insecticide pirimiphos-methyl (Actellic 300CS), during the 2018 IRS round on Bioko Island, Equatorial Guinea. Approximately 60 SOs sprayed a total of 67,721 structures in 16,653 houses during the round. Houses that were reportedly sprayed were randomly selected for quality control testing. The SOs were monitored twice in 2018, an initial screening in March followed by sharing of results with the IRS management team and identification of SOs to be re-trained, and a second screening in June to monitor the effectiveness of training. Insecticide samples were adhesive-lifted from wooden and cement structures and analysed using HPLC. Results The study suggests that with adequate quality control measures and refresher training, suboptimal spraying was curtailed, with a significant increased concentration delivered to the bedroom (difference = 0.36, P 

Abstract Background Malaria has a considerable impact on the health of the populations of developing countries; indeed, the entire population of Rwanda is at risk of contracting the disease. Although various interventions to control malaria have been implemented in Rwanda, the incidence of malaria has increased since 2012. There is an interest in understanding factors driving its persistence in Rwanda. This study aims at evaluating the effect of socio-economic and environmental factors, seasonality and the use of insecticide-treated mosquito nets (ITNs) on malaria persistence in Rwanda. Methods This study analysed data from the 2014–2015 Rwanda Demographic and Health Survey of 11,202 household’s members composed of children under the age of 5 and women aged between 15 and 49. Bivariate analysis was performed between the outcome and each covariate including wealth, altitude, education level, place of residence, and use of ITNs generating percentages. Chi square test was performed to compare malaria negatives and positives on each covariate. Significant variables were subjected to logistic regression analysis to evaluate factors that are significantly associated with malaria at P 

Kuehn BM.

A large Swedish study published in PLOS Medicine appears to debunk the idea that either elective or nonelective cesarean delivery increases the risk that a child will develop obesity.

Kuehn BM.

Urgent action is needed to meet the Paris Agreement climate goals to limit the potential health impacts on children worldwide, according to a statement from 120 international climate experts.

Kuehn BM.

Researchers have reported that a new vaccine against the dengue virus protected children and adolescents in a phase 3 trial conducted in Asia and Latin America.

Snyder RA.

In this narrative medicine essay, a surgical oncologist recalls helping her mother through her treatment and death from lung cancer and tells of the lesson she brought back to her own practice from the experience that the essence of clinical care is human connection: the ability to listen to others, witness their suffering, hear their joy, and be present in their company.

Cleary E.

Cherry blossoms line the Saturday Market near Burnside. Back home, winter…

Desai AN.

This JAMA Patient Page describes cryptosporidiosis, its symptoms, diagnosis, treatment, and prevention methods.

Steinberg JS, Shabanov V, Ponomarev D, et al.

This randomized trial compares the effects of pulmonary vein isolation with vs without renal denervation on freedom from atrial fibrillation, atrial flutter, or atrial tachycardia at 1 year among patients with atrial fibrillation and hypertension.

Issa Y, Kempeneers MA, Bruno MJ, et al.

This randomized clinical trial compares the effects of pancreatic drainage surgery within 6 weeks vs a stepped medical-endoscopy-surgical approach on pain score and relief over 18 months among patients with chronic pancreatitis.

Futier E, Garot M, Godet T, et al.

This randomized clinical trial assesses the effect of hydroxyethyl starch 130/0.4 (HES) vs normal saline for intravascular volume expansion in patients at risk of postoperative kidney injury on mortality and postoperative complications up to 14 days after major abdominal surgery.

Matta MK, Florian J, Zusterzeel R, et al.

This randomized clinical trial assesses the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in lotion, aerosol spray, nonaerosol spray, and pump spray sunscreen products under single- and maximal-use conditions.

Glazier A, Mone T.

In Reply In our Viewpoint on the success of opt-in organ donation policy in the United States, we reviewed organ donation rates from opt-in and opt-out legal jurisdictions to provide a high-level comparison between these 2 authorization strategies. The rate was calculated as donors per 10 000 deaths, not donors per potential eligible donor as incorrectly stated by Dr Wall and colleagues. Donors per deaths is the best available data for an international comparison.

Miller BJ, Slota JM, Ehrenfeld JM.

In Reply Regarding our Viewpoint on price transparency in EHRs, Dr Cho and colleagues suggest that clinicians are not adequately trained to discuss costs with patients. While we agree that clinicians are not traditionally trained to discuss costs with patients, these discussions are already occurring. Many patients face significant financial burdens affecting access; transparency merely provides information to help make decisions currently made in a vacuum.

Mummadi SR, Mishra R, Mummadi RR.

To the Editor A Viewpoint proposed implementing price transparency for physicians in EHRs as a means of achieving cost-conscious care.

Tarzi C, Tarzi G, Walker M, et al.

This study uses data from the 2019 Fédération Internationale de Football Association Women’s World Cup to determine the incidence rate and subsequent medical assessment of head collision events.

Olfson M, Zhang V, Schoenbaum M, et al.

This study assessed the number of individuals receiving treatment for opioid use disorder in the United States by age group and sex using a national prescription database to compare between the number of buprenorphine prescriptions filled and the number of US opioid-related overdose deaths.

Asclepius, Asclepios, Asklepios, Aesculapius (Latin), or Ασκληπιος (Greek), if one has a yearning for the good old days of resinated wine and chariot races, is probably the most venerated physician of all times. Scholia in Homer’s Iliad suggests that the name Asklepios was derived from words meaning applying (askein) and making the limbs gentle (epia). Another interpretation ascribes his name to “healing soothingly and for deferring the withering that comes with death.” Yet a third writer affirms that Asklepios was originally known as Epios because of his gentleness and calmness. After he had cured Askles, the tyrant of Epidaurus who suffered from ophthalmia, he was called Asklepios, with the accent on the penult. Demosthenes changed the pronunciation by accenting the antepenult. Asclepius is to be distinguished from Asclepiad, a generic appellation for a priest of the temple of Asclepius, from Asclepias, a genus of Asclepiadaceous plants, and from Asclepiades, a Bithynian physician of the second century, B. C., who practiced in Rome and openly admitted opposition to the teachings of Hippocrates.

Butler SM.

The growing interest in addressing social determinants of health—nonclinical factors influencing health—raises practical issues about the way we budget for collaborative efforts across governmental departments. In particular, the expanding research on the relationship between such factors as housing, transportation, and community services and the health condition of many households indicates the importance of giving program leaders the flexibility and incentive to coordinate resources from multiple sources.

Voelker R.

The first test to aid in screening newborns for Duchenne muscular dystrophy (DMD) has received FDA authorization for marketing.

Voelker R.

A new app will allow health professionals to share how they’ve used FDA-approved drugs for off-label indications with patients who have difficult-to-treat infectious diseases. The internet-based repository, called CURE ID, is a collaboration between the FDA and the National Center for Advancing Translational Sciences, which is part of the National Institutes of Health (NIH).

Voelker R.

The FDA has authorized a new diagnostic test based on bacteriophage technology to detect methicillin-resistant Staphylococcus aureus (MRSA) colonization more quickly than traditional culture-based techniques allow.

Estes N, III.

Atrial fibrillation and hypertension represent 2 of the most important national public health priorities. Atrial fibrillation is the most common sustained cardiac arrhythmia among adults, affecting up to 2% of the US population. The prevalence of atrial fibrillation is expected to increase 3-fold in the next 3 decades. Robust data have identified hypertension as an independent modifiable risk factor for atrial fibrillation and as the most common cardiovascular condition associated with it. Hypertension is present in up to 80% of individuals with atrial fibrillation. Fulfilling a fundamental principle of evidence-based medicine, current therapeutic strategies to maintain sinus rhythm have a firm foundation in appropriately designed clinical trials. Lifestyle modification, treatment with antiarrhythmic and antihypertensive drugs, and pulmonary vein isolation have been established as approaches to relieve the burden of atrial fibrillation and improve outcomes. Despite considerable progress in prevention and treatment, atrial fibrillation continues to impose a significant economic and disability burden in the United States and worldwide. Robust data from clinical trials for the treatment of atrial fibrillation clarifying the risks and benefits of pulmonary vein isolation have resulted in recent expansion of catheter ablation as a guideline-directed approach for select patient populations.

Adamson AS, Shinkai K.

UV radiation is the most important known modifiable risk factor for the development of skin cancer including melanoma. Behavioral measures to reduce this risk factor include seeking shade, wearing hats and protective clothing, avoiding outdoor activities during peak sunlight hours, and regularly using sunscreen. Sunscreen ingredients fall into 2 distinct categories: mineral or chemical. Mineral sunscreens contain physical UV filters, such as zinc oxide and titanium dioxide, that offer broad-spectrum UV coverage by reflecting or refracting UV radiation from skin. Chemical sunscreens contain UV filters that absorb UV radiation and, when used in combination, can provide equal if not superior broad-spectrum UV filtration compared with mineral sunscreens. Chemical sunscreens are less likely to leave chalky or tinted white residue on the skin, which is more cosmetically acceptable especially on darker skin types. Given these relative advantages, chemical sunscreens are found in the majority of commonly available sunscreen formulations within the $1.95 billion sun care industry in the United States.

Zampieri FG, Cavalcanti AB.

Hydroxyethyl starch (HES) solutions have had a turbulent history as resuscitation fluids. There was initial optimism that these products would efficiently expand the intravascular space with a prolonged intravascular half-life and therefore would be “volume sparing,” with less edema. However, enthusiasm was tempered when HES solutions were reported to be harmful when administered to critically ill patients, including those with sepsis. Despite these concerns, HES is still used in surgery under the premise that lower doses infused under strict protocols would be safe. In this issue of JAMA, Futier and colleagues report the results of the FLASH multicenter randomized clinical trial, which assessed the effects of HES vs saline for fluid resuscitation in patients undergoing major abdominal surgery. The primary end point was a composite of death and occurrence of renal, respiratory, cardiovascular, infectious, or surgical complications. Several secondary and exploratory end points were also reported.

Hines O.

Chronic pancreatitis is characterized by pancreatic endocrine and exocrine insufficiency, along with persistent, and in some cases, unrelenting pain. While pancreatic insufficiency is effectively managed with pharmacologic intervention, the pain associated with this condition is difficult to control and commonly leads to severe consequences for the patient. A search of ClinicalTrials.gov for chronic pancreatitis revealed 152 studies, nearly all of which consist of interventions for pain. The current modalities, including pain medication, pancreatic enzyme replacement, behavioral therapy, endoscopic treatment, and surgery, all have varying degrees of efficacy. Less-invasive modalities include endoscopic retrograde pancreatography (ERP) with stone extraction, ERP with endoscopic lithotripsy and stent placement, and extracorporeal shock wave lithotripsy (ESWL). Surgical interventions include drainage procedures with attachment of the main pancreatic duct to the intestine or resection of the involved pancreas.

In the Research Letter entitled “Prevalence of Oral HPV Infection in Unvaccinated Men and Women in the United States, 2009-2016” published in the September 10, 2019, issue of JAMA, data were incorrect in the Table and the Discussion section of the text. In the Table, in the “2015-2016” column of the “Women, %” section, the values reported for black, non-Hispanic women and Hispanic women were transposed; the value for black, non-Hispanic women should have been reported as 13.4 and the value for Hispanic women as 17.8. In the first sentence of the Discussion section, the value reported as 37% should have been 38%. This article has been corrected online.

In the Original Investigation entitled “Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial” published in the November 12, 2019, issue of JAMA, a value was incorrect in the text. In the last sentence of the Results section, the value reported as 0.5 for mean creatinine concentration should have been reported as 0.05. This article has been corrected online.

Abbasi J.

This Medical News article is an interview with the American Heart Association’s Rose Marie Robertson, MD, about the explosion of electronic cigarette use among young people.

Basch E, Wilfong L, Schrag D.

This Viewpoint discusses barriers to collecting patient-reported outcome measures for symptom monitoring as a component of the Oncology Care First payment model, a Centers for Medicare & Medicaid Services program that provides bundled population payments to cover physician services and enhancements intended to improve care quality for patients receiving systemic cancer treatment, and proposes ways to implement and facilitate the requirement given its importance to patient well-being.

Kho KA, Shields JK.

This JAMA Insights Women’s Health reviews the epidemiology, evaluation, and management of primary dysmenorrhea, with a focus on use of combined hormonal oral contraceptive pills for symptom management.

Douglass LA, Davis AM.

This JAMA Clinical Guidelines Synopsis summarizes the United Kingdom 2018 National Institute for Health and Care Excellence (NICE) guideline on the assessment and management of heavy menstrual bleeding.

Carnethon MR, Kershaw KN, Kandula NR.

This Viewpoint discusses the position of the National Institutes of Health (NIH) regarding disparities in health and research and offers recommendations that could hasten progress in eliminating disparities on the basis of race/ethnicity, sex, and socioeconomic status.

Zhang Z, Chung H, Gong T.

A 61-year-old woman who had immigrated from Micronesia 10 years ago had 1 month of sharp, progressive, intermittent, nonradiating right upper quadrant abdominal pain; she was febrile, had leukocytosis and elevated levels of liver panel analytes, and endoscopic retrograde cholangiopancreatography showed numerous worms in the biliary trees. What is the diagnosis and what would you do next?…

Abstract Background Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published. Case presentation A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free. Conclusions We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.…

Abstract Background The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay. Methods ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2–3, ≤ 2 log10 copies/106 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log10 copies/106 PBMCs) at week 96 were evaluated using a logistic regression model. Results Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log10 copies/106 PBMCs, P 

Abstract Background The aim of our study was to analyze the risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease (CHD). Methods We performed a retrospective cohort study, and children with CHD who underwent open-heart surgeries at Shanghai Children’s Medical Center from January 1, 2012 to December 31, 2018 were included. The baseline characteristics of these patients of different ages, including neonates (0–1 months old), infants (1–12 months old) and children (1–10 years old), were analyzed, and the association of risk factors with postoperative nosocomial infection were assessed. Results A total of 11,651 subjects were included in the study. The overall nosocomial infection rate was 10.8%. Nosocomial infection rates in neonates, infants, and children with congenital heart disease were 32.9, 15.4, and 5.2%, respectively. Multivariate logistic regression analysis found age (OR 0798, 95%CI: 0.769–0.829; P 

Abstract Background The immune response during falciparum malaria mediates both harmful and protective effects on the host; however the participating molecules have not been fully defined. Interleukin (IL)-27 is a pleiotropic cytokine exerting both inflammatory and anti-inflammatory effects, but data on IL-27 in malaria patients are scarce. Methods Clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) HIV-1 co-infection, from HIV-infected patients with similar symptoms without malaria (n = 58) and from healthy controls (n = 52). In vitro studies were performed in endothelial cells and PBMC using hemozoin crystals. Samples were analyzed using enzyme immunoassays and quantitative PCR. Results (i) IL-27 was markedly up-regulated in malaria patients compared with controls and HIV-infected patients without malaria, showing no relation to HIV co-infection. (ii) IL-27 was correlated with P. falciparum parasitemia and von Willebrand factor as a marker of endothelial activation, but not with disease severity. (iii) In vitro, IL-27 modulated the hemozoin-mediated cytokine response in endothelial cells and PBMC with enhancing effects on IL-6 and attenuating effects on IL-8. Conclusion Our findings show that IL-27 is regulated during falciparum malaria, mediating both inflammatory and anti-inflammatory effects, potentially playing an immune-regulatory role during falciparum malaria.…

Abstract Background Timely infant testing for HIV is critical to ensure optimal treatment outcomes among exposed infants. While world health organization recommends HIV exposed infants to be tested between 4 to 6 weeks of age, in developing countries like Ethiopia, access to timely infant testing is still very limited. The study is intended to assess timely infant testing, testing for HIV at the 18th month, test results and factors influencing HIV positivity among infants born to HIV positive mothers in public hospitals of Mekelle, Ethiopia. Methods A cross-sectional study design was employed on 558 HIV exposed infants, using consecutive sampling technique. A checklist was used to extract 4 years (January 2014–December 2017) secondary data, collected from January–April 2018. Data were analyzed using SPSS version 20, and binary logistic regression model was used to examine the association of independent variables with the outcome variables. Results Timely infant testing for HIV accounted for 346(62.0%). Mothers who attended antenatal care (AOR: 2.77; 95% CI: 1.17, 6.55) and who were counselled on feeding options (AOR: 2.01; 95% CI: 1.11, 3.65) were strongly associated with timely infant testing. Poor maternal adherence status was associated with infants’ HIV positivity at the 18th month of antibody test (AOR: 15.93; 95% CI: 2.21, 94.66). Being rural resident (AOR: 4.0; 95% CI: 1.23, 13.04), being low birth weight (AOR: 5.64; 95% CI: 2.00, 16.71) and not receiving ARV prophylaxis (AOR: 4.70; 95% CI: 1.15, 19.11) were positively associated with the overall HIV positivity. Conclusions A considerable proportion of exposed infants did not undergo timely testing for HIV. Antenatal care follow-up and counselling on feeding options were associated with timely infant testing. Mother’s poor adherence status was associated with infant’s HIV positivity at the 18th month of antibody testing. Being rural resident, being low birth weight, and not receiving ARV prophylaxis were the factors that enhance the overall HIV positivity. Timely infant testing, counselling on feeding options and adherence should be intensified, and prevention of mother-to-child transmission program in rural settings need to be strengthened.…

Following publication of the original article [1], it was brought to the authors’ attention that one of the names in the author list had been provided with the incorrect spelling.…

Abstract Background Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal. Methods Clustering of infection was defined by the percent of persons with positive slides for asexual P. falciparum sleeping in a house which had been geopositioned. Data from each site were then tested for spatial, temporal and spatio-temporal clustering in relation to the prevalence of infection from smear surveys. Results These studies suggest that clustering of P. falciparum infection also affects the effectiveness of control interventions. For example, the clustering of infection in Madina Fall disappeared in 2014–2016 after vector control eliminated the only breeding site in 2013. In contrast, the temporal clustering of infection in Dioro (rainy season of 2014, dry season of 2015) was consistent with the loss of funding for Dioro in the second quarter of 2014 and disappeared when funds again became available in late 2015. The clustering of infection in rural (western) areas of Gambissara was consistent with known rural–urban differences in the prevalence of infection and with the thatched roofs, open eaves and mud walls of houses in rural Gambissara. In contrast, the most intense transmission was in Dangassa, where the only encouraging observation was a lower prevalence of infection in the dry season. Taken together, these results suggest: (a) the transmission of infection was stopped in Madina Fall by eliminating the only known breeding site, (b) the prevalence of infection was reduced in Dioro after financial support became available again for malaria control in the second half of 2015, (c) improvements in housing should improve malaria control by reducing the number of vectors in rural communities such as western Gambissara, and (d) beginning malaria control during the dry season may reduce transmission in hyperendemic areas such as Dangassa. Conclusions From a conceptual perspective, testing for spatial, temporal and spatio-temporal clustering based on epidemiologic data permits the generation of hypotheses for the clustering observed and the testing of candidate interventions to confirm or refute those hypotheses.…

Ramirez V, Sladek J, Godinez D, et al.

AbstractNeurons are an integral component of the immune system that functions to coordinate responses to bacterial pathogens. Sensory nociceptive neurons that can detect bacterial pathogens are found throughout the body with dense innervation of the intestinal tract. Here we assessed the role of these nerves in the coordination of host defenses to Citrobacter rodentium. Selective ablation of nociceptive neurons significantly increased bacterial burden 10 days post infection and delayed pathogen clearance. Since the sensory neuropeptide CGRP regulates host-responses during infection of the skin, lung, and small intestine, we assessed the role of CGRP receptor signaling during C. rodentium infection. Although CGRP receptor blockade reduced certain pro-inflammatory gene expression, bacterial burden and Il-22 expression was unaffected. Our data highlight that sensory nociceptive neurons exert a significant host protective role during C. rodentium infection, independent of CGRP receptor signaling.

Dezanet L, Maylin S, Gabassi A, et al.

AbstractBackgroundTo describe the kinetics of hepatitis B core-related antigen (qHBcrAg) and anti-hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF)-treatment and assess their ability to predict HBeAg-seroclearance in patients co-infected with HIV and hepatitis B virus (HBV).MethodsSerum qHBcrAg, qAnti-HBc and HBV-DNA were obtained at TDF-initiation and every 6-12 months. On-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HR) assessing the association between markers and HBeAg-seroclearance were calculated using proportional hazards regression and sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg-seroclearance were assessed using time-dependent ROC curves.ResultsDuring a median 4.6 years, cumulative incidence of HBsAg-seroclearance and HBeAg-seroclearance were 3.2% (n=5/158) and 27.4% (n=26/95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive (-0.051 and -0.011 log10U/mL/month during 18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg-status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg-seroclearance (adjusted-HR=0.48/log10U/mL; 95%CI=0.33-0.70 and unadjusted-HR=1.49/log10PEIU/mL; 95%CI=1.08-2.07, respectively). Cutoffs with the highest accuracy in predicting HBeAg-seroclearance at 36 months were qHBcrAg4.1 log10PEIU/mL (Se=0.42/Sp=0.81).ConclusionsIn co-infected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg-seroclearance.

Costantini V, Cooper E, Hardaker H, et al.

AbstractBACKGROUNDMost information on mucosal and systemic immune response to norovirus infection is derived from human challenge studies, birth cohort studies, or vaccine trials in healthy adults. However, few data are available on immune responses to norovirus in the elderly.MATERIALSTo study the mucosal and systemic immune response against norovirus, 43 long-term care facilities (LTCFs) were enrolled prospectively in 2010-2014. Baseline saliva samples were collected from 17 facilities and from cases and controls up to day 84 from 10 outbreaks as well as acute and convalescent sera.RESULTSNorovirus-specific IgA levels in baseline saliva samples were low and increased in both symptomatic patients and asymptomatic shedders at day 5 after onset. ROC analysis correctly assigned prior norovirus infection in 23 (92%) of 25 participants. Cases and asymptomatic shedders showed seroconversion for IgG (80%), IgA (78%) and blockade antibodies (87%). Salivary IgA levels strongly correlated with increased convalescent serum IgA titers and blockade antibodies.CONCLUSIONSSalivary IgA levels strongly correlated with serum IgA titers and blockade antibodies and remained elevated 3 months after a norovirus outbreak. A single salivary sample collected on day 14 could be used to identify recent infection in a suspected outbreak or to monitor population salivary IgA.

McMahon J, Hoy J.

Strunk T, Hibbert J, Doherty D, et al.

AbstractBackgroundLate-onset sepsis (LOS) with Staphylococcus epidermidis is common in preterm infants, but the immunological mechanisms underlying heightened susceptibility are poorly understood.AimTo characterise the ontogeny of cytokine responses to live S. epidermidis in preterm infants with and without subsequent Gram-positive LOS.MethodsA prospective observational cohort study of preterm infants (

Eaton E.

medications for opioid use disorder (MOUD)HIVrapid startpersons who inject drugsendocarditis…

Barocas J, Morgan J, Wang J, et al.

AbstractBackgroundEndocarditis, once predominately found in older adults, is increasingly common among younger persons who inject drugs. Untreated opioid use disorder (OUD) complicates endocarditis management. We aimed to determine if rates of overdose and rehospitalization differ between persons with OUD with endocarditis who are initiated on medications for OUD (MOUDs) within 30 days of hospital discharge and those who are not.MethodsWe performed a retrospective cohort study using a large commercial health insurance claims database of persons 18 years and older between July 1, 2010 and June 30, 2016. Primary outcomes included opioid-related overdoses and 1-year all-cause rehospitalization. We calculated incidence rates for the primary outcomes and developed Cox hazards models to predict time from discharge to each primary outcome as a function of receipt of MOUDs.ResultsThe cohort included 768 individuals (mean age 39 years, 51% male). Only 5.7% of people received MOUDs in the 30 days following hospitalization. The opioid-related overdose rate among those who did receive MOUDs in the 30 days following hospitalization was lower than among those who did not (5.8 per 100 person-years (95% CI, 5.1-6.4) vs. 7.3 per 100-person years (95% CI, 7.1-7.5), respectively). The rate of one-year rehospitalization among those who received MOUDs was also lower than those who did not (162.0 per 100 person-years (95% CI, 157.4-166.6) vs 255.4 per 100 person-years (95% CI, 254.0-256.8), respectively). In the Cox hazards models, the receipt of MOUDs was not associated with either of the outcomes.ConclusionsMOUD receipt following endocarditis may improve important health-related outcomes in commercially-insured persons with OUD.