Publications by authors named "Barbara Willey"

84 Publications

Improving maternal and newborn health services in Northeast Nigeria through a government-led partnership of stakeholders: a quasi-experimental study.

BMJ Open 2022 02 1;12(2):e048877. Epub 2022 Feb 1.

London School of Hygiene & Tropical Medicine, London, UK.

Objectives: This study aimed to quantify change in the coverage, quality and equity of essential maternal and newborn healthcare interventions in Gombe state, Northeast Nigeria, following a four year, government-led, maternal and newborn health intervention.

Design: Quasi-experimental plausibility study. Repeat cross-sectional household and linked health facility surveys were implemented in intervention and comparison areas.

Setting: Gombe state, Northeast Nigeria.

Participants: Each household survey included a sample of 1000 women aged 13-49 years with a live birth in the previous 12 months. Health facility surveys comprised a readiness assessment and birth attendant interview.

Interventions: Between 2016-2019 a complex package of evidence-based interventions was implemented to increase access, use and quality of maternal and newborn healthcare, spanning the six WHO health system building blocks.

Outcome Measures: Eighteen indicators of maternal and newborn healthcare.

Results: Between 2016 and 2019, the coverage of all indicators improved in intervention areas, with the exception of postnatal and postpartum contacts, which remained below 15%. Greater improvements were observed in intervention than comparison areas for eight indicators, including coverage of at least one antenatal visit (71% (95% CI 62 to 68) to 88% (95% CI 82 to 93)), at least four antenatal visits (46% (95% CI 39 to 53) to 69% (95% CI 60 to 75)), facility birth (48% (95% CI 37 to 59) to 64% (95% CI 54 to 73)), administration of uterotonics (44% (95% CI 34 to 54) to 59% (95% CI 50 to 67)), delayed newborn bathing (44% (95% CI 36 to 52) to 62% (95% CI 52 to 71)) and clean cord care (42% (95% CI 34 to 49) to 73% (95% CI 66 to 79)). Wide-spread inequities persisted however; only at least one antenatal visit saw pro-poor improvement.

Conclusions: This intervention achieved improvements in life-saving behaviours for mothers and newborns, demonstrating that multipartner action, coordinated through government leadership, can shift the needle in the right direction, even in resource-constrained settings.
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http://dx.doi.org/10.1136/bmjopen-2021-048877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808391PMC
February 2022

'A seamless transition': how to sustain a community health worker scheme within the health system of Gombe state, northeast Nigeria.

Health Policy Plan 2021 Aug;36(7):1067-1076

London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Health interventions introduced as part of donor-funded projects need careful planning if they are to survive when donor funding ends. In northeast Nigeria, the Gombe State Primary Health Care Development Agency and implementing partners recognized this when introducing a Village Health Worker (VHW) Scheme in 2016. VHWs are a new cadre of community health worker, providing maternal, newborn and child health-related messages, basic healthcare and making referrals to health facilities. This paper presents a qualitative study focussing on the VHW Scheme's sustainability and, hence, contributes to the body of literature on sustaining donor-funded interventions as well as presenting lessons aimed at decision-makers seeking to introduce similar schemes in other Nigerian states and in other low- and middle-income settings. In 2017 and 2018, we conducted 37 semi-structured interviews and 23 focus group discussions with intervention stakeholders and community members. Based on respondents' accounts, six key actions emerged as essential in promoting the VHW Scheme's sustainability: government ownership and transition of responsibilities, adapting the scheme for sustainability, motivating VHWs, institutionalizing the scheme within the health system, managing financial uncertainties and fostering community ownership and acceptance. Our study suggests that for a community health worker intervention to be sustainable, reflection and adaption, government and community ownership and a phased transition of responsibilities are crucial.
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http://dx.doi.org/10.1093/heapol/czab063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359746PMC
August 2021

Dissemination of Verona Integron-encoded Metallo-β-lactamase among clinical and environmental Enterobacteriaceae isolates in Ontario, Canada.

Sci Rep 2020 10 29;10(1):18580. Epub 2020 Oct 29.

Public Health Ontario Laboratory, Toronto, ON, Canada.

Surveillance data from Southern Ontario show that a majority of Verona Integron-encoded Metallo-β-lactamase (VIM)-producing Enterobacteriaceae are locally acquired. To better understand the local epidemiology, we analysed clinical and environmental bla-positive Enterobacteriaceae from the area. Clinical samples were collected within the Toronto Invasive Bacterial Diseases Network (2010-2016); environmental water samples were collected in 2015. We gathered patient information on place of residence and hospital admissions prior to the diagnosis. Patients with and without plausible source of acquisition were compared regarding risk exposures. Microbiological isolates underwent whole-genome sequencing (WGS); bla carrying plasmids were characterized. We identified 15 patients, thereof 11 with bla-positive Enterobacter hormaechei within two genetic clusters based on WGS. Whereas no obvious epidemiologic link was identified among cluster I patients, those in cluster II were connected to a hospital outbreak. Except for patients with probable acquisition abroad, we did not identify any further risk exposures. Two bla-positive E. hormaechei from environmental waters matched with the clinical clusters; plasmid sequencing suggested a common ancestor plasmid for the two clusters. These data show that both clonal spread and horizontal gene transfer are drivers of the dissemination of bla-carrying Enterobacter hormaechei in hospitals and the aquatic environment in Southern Ontario, Canada.
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http://dx.doi.org/10.1038/s41598-020-75247-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596063PMC
October 2020

Provision of essential evidence-based interventions during facility-based childbirth: cross-sectional observations of births in northeast Nigeria.

BMJ Open 2020 10 23;10(10):e037625. Epub 2020 Oct 23.

Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK.

Objectives: To measure the provision of evidence-based preventive and promotive interventions to women, and subsequently their newborns, during childbirth in a high-mortality setting.

Design And Participants: Cross-sectional observations of care provided to women, and their newborns during the intrapartum and immediate postpartum period using a standardised checklist capturing healthcare worker behaviours regarding lifesaving and respectful care.

Setting: Ten primary healthcare facilities in Gombe state, northeast Nigeria. The northeast region of Nigeria has some of the highest maternal and newborn death rates globally.

Main Outcome Measures: Data on 50 measures of internationally recommended evidence-based interventions and good practice.

Results: 1875 women were admitted to a health facility during the observation period; of these, 1804 gave birth in the facility and did not experience an adverse event or death. Many clinical interventions around the time of birth were routinely implemented, including provision of uterotonic (96% (95% CI 93% to 98%)), whereas risk-assessment measures, such as history-taking or checking vital signs were rarely completed: just 2% (95% CI 2% to 7%) of women had their temperature taken and 12% (95% CI 9% to 16%) were asked about complications during the pregnancy.

Conclusions: The majority of women did not receive the recommended routine processes of childbirth care they and their newborns needed to benefit from their choice to deliver in a health facility. In particular, few benefited from even basic risk assessments, leading to missed opportunities to identify risks. To continue with the recommendation of childbirth care in primary healthcare facilities in high mortality settings like Gombe, it is crucial that birth attendant capacity, capability and prioritisation processes are addressed.
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http://dx.doi.org/10.1136/bmjopen-2020-037625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590366PMC
October 2020

Household Transmission of Carbapenemase-producing Enterobacterales in Ontario, Canada.

Clin Infect Dis 2021 12;73(11):e4607-e4615

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Background: Data on household transmission of carbapenemase-producing Enterobacterales (CPE) remain limited. We studied risk of CPE household co-colonization and transmission in Ontario, Canada.

Methods: We enrolled CPE index cases (identified via population-based surveillance from January 2015 to October 2018) and their household contacts. At months 0, 3, 6, 9, and 12, participants provided rectal and groin swabs. Swabs were cultured for CPE until September 2017, when direct polymerase chain reaction (PCR; with culture of specimens if a carbapenemase gene was detected) replaced culture. CPE risk factor data were collected by interview and combined with isolate whole-genome sequencing to determine likelihood of household transmission. Risk factors for household contact colonization were explored using a multivariable logistic regression model with generalized estimating equations.

Results: Ninety-five households with 177 household contacts participated. Sixteen (9%) household contacts in 16 (17%) households were CPE-colonized. Household transmission was confirmed in 3/177 (2%) cases, probable in 2/177 (1%), possible in 9/177 (5%), and unlikely in 2/177 (1%). Household contacts were more likely to be colonized if they were the index case's spouse (odds ratio [OR], 6.17; 95% confidence interval [CI], 1.05-36.35), if their index case remained CPE-colonized at household enrollment (OR, 7.00; 95% CI, 1.92-25.49), or if they had at least 1 set of specimens processed after direct PCR was introduced (OR, 6.46; 95% CI, 1.52-27.40).

Conclusions: Nine percent of household contacts were CPE-colonized; 3% were a result of household transmission. Hospitals may consider admission screening for patients known to have CPE-colonized household contacts.
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http://dx.doi.org/10.1093/cid/ciaa1295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662791PMC
December 2021

Evaluation of a capacity building intervention on malaria treatment for under-fives in rural health facilities in Niger State, Nigeria.

Malar J 2020 Feb 24;19(1):90. Epub 2020 Feb 24.

Disease Control Department, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

Background: Despite the uptake of parasitological testing into policy and practice, appropriate prescription of anti-malarials and artemisinin-based combination therapy (ACT) in accordance with test results is variable. This study describes a National Malaria Control Programme-led capacity building intervention which was implemented in 10 States of Nigeria. Using the experience of Niger State, this study assessed the effect on malaria diagnosis and prescription practices among febrile under-fives in rural health facilities.

Methods: The multicomponent capacity building intervention consisted of revised case management manuals; cascade training from national to state level carried out at the local government area (LGA) level; and on the job capacity development through supportive supervision. The evaluation was conducted in 28, principally government-owned, health facilities in two rural LGAs of Niger State, one in which the intervention case management of malaria was implemented and the other acted as a comparison area with no implementation of the intervention. Three outcomes were considered in the context of rapid diagnostic testing (RDT) for malaria which were: the prevalence of RDT testing in febrile children; appropriate treatment of RDT-positive children; and appropriate treatment of RDT-negative children. Outcomes were compared post-intervention between intervention and comparison areas using multivariate logistic regression.

Results: The intervention did not improve appropriate management of under-fives in intervention facilities above that seen for under-fives in comparison facilities. Appropriate treatment with artemisinin-based combinations of RDT-positive and RDT-negative under-fives was equally high in both areas. However, appropriate treatment of RDT-negative children, when defined as receipt of no ACT or any other anti-malarials, was better in comparison areas. In both areas, a small number of RDT-positives were not given ACT, but prescribed an alternative anti-malarial, including artesunate monotherapy. Among RDT-negatives, no under-fives were prescribed artesunate as monotherapy.

Conclusion: In a context of significant stock-outs of both ACT medicines and RDTs, under-fives were not more appropriately managed in intervention than comparison areas. The malaria case management intervention implemented through cascade training reached only approximately half of health workers managing febrile under-fives in this setting. Implementation studies on models of cascade training are needed to define what works in what context.
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http://dx.doi.org/10.1186/s12936-020-03167-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041190PMC
February 2020

Emerging antimicrobial resistance among strains in bloodstream infections in Toronto, 2006-2016: a retrospective cohort study.

CMAJ Open 2018 Oct-Dec;6(4):E580-E586. Epub 2018 Dec 3.

Department of Microbiology (Mineau, Kozak, Kissoon, Paterson, Oppedisano, Douri, Gogan, Willey, McGeer, Poutanen), University Health Network/Sinai Health System, Toronto, Ont.; Centre intégré de santé et de services sociaux de Chaudière-Appalaches (Mineau), Sainte-Marie, Que.; Lawrence Park Collegiate Institute (Gogan); Departments of Laboratory Medicine and Pathobiology and of Medicine (McGeer, Poutanen), University of Toronto, Toronto, Ont.

Background: Enterobacteriaceae that produce extended-spectrum β-lactamase (ESBL) have emerged as a serious threat, with variable rates depending on geographic region. We determined the prevalence of ESBL-producing , , and in bloodstream infections in Toronto from 2006 through 2016.

Methods: All patients with , , and isolated from blood in a tertiary care microbiology laboratory in Toronto between 2006 and 2016 (1 isolate per species per patient per year) were included in this retrospective cohort study. Organisms were identified by conventional methods, and susceptibility testing was performed according to Clinical and Laboratory Standards Institute standards. Screening for ESBL and phenotypic confirmatory testing were done with a modified Clinical and Laboratory Standards Institute method. ST131 clonal type was determined by means of an established protocol.

Results: The proportion of ESBL-producing isolates increased significantly between 2006 and 2016, from 6.4% (19/296) to 17.3% (89/513) ( < 0.001). This trend was seen in both intensive care units and emergency departments. Concurrently, the proportion of ST131 among ESBL-producing also increased significantly, from 31.6% (6/19) in 2006 to 73.0% (65/89) in 2016 ( = 0.03). Among ESBL-producing significant resistance was noted to multiple antimicrobial classes. Comparable increases in the proportion of ESBL-producing , and were not noted.

Interpretation: We observed a significant increase in the proportion of ESBL-producing in bloodstream infections in Toronto temporally correlated with an increase in the ST131 clonal type. Recognition of this dramatic rise is important to inform empiric antibiotic treatment.
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http://dx.doi.org/10.9778/cmajo.20180039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277254PMC
December 2018

Correlates of the Women's Development Army strategy implementation strength with household reproductive, maternal, newborn and child healthcare practices: a cross-sectional study in four regions of Ethiopia.

BMC Pregnancy Childbirth 2018 Sep 24;18(Suppl 1):373. Epub 2018 Sep 24.

Last 10 Kilometers Project (L10K) 2020, JSI Research & Training Institute, Inc, Bole Sub-City, Kebele 03/05, Hs #, 2111, Addis Ababa, Ethiopia.

Background: To address the shortfall in human resources for health, Ethiopia launched the Health Extension Program (HEP) in 2004, establishing a health post with two female health extension workers (HEWs) in every kebele (community). In 2011, the Women's Development Army (WDA) strategy was added, using networks of neighboring women to increase the efficiency of HEWs in reaching every household, with one WDA team leader for every 30 households. Through the strategy, women in the community, in partnership with HEWs, share and learn about health practices and empower one another. This study assessed the association between the WDA strategy implementation strength and household reproductive, maternal, newborn and child health care behaviors and practices.

Methods: Using cross-sectional household surveys and community-level contextual data from 423 kebeles representing 145 rural districts, an internal comparison group design was applied to assess whether HEP outreach activity and household-level care practices were better in kebeles with a higher WDA density. The density of active WDA leaders was considered as WDA strategy implementation strength; higher WDA density in a kebele indicating relatively high implementation strength. Based on this, kebeles were classified as higher, moderate, or lower. Multilevel logit models, adjusted for respondents' individual, household and contextual characteristics, were used to assess the associations of WDA strategy implementation strength with outcome indicators of interest.

Results: Average numbers of households per active WDA team leader in the 25th, 50th and 75th percentiles of the kebeles studied were respectively 41, 50 and 73. WDA density was associated with better service for six of 13 indicators considered (p < 0.05). For example, kebeles with one active WDA team leader for up to 40 households (higher category) had respectively 7 (95% CI, 2, 13), 11 (5, 17) and 9 (1, 17) percentage-points higher contraceptive prevalence rate, coverage of four or more antenatal care visits, and coverage of institutional deliveries respectively, compared with kebeles with one active WDA team leader for 60 or more households (lower category).

Conclusion: Higher WDA strategy implementation strength was associated with better health care behaviors and practices, suggesting that the WDA strategy supported HEWs in improving health care services delivery.
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http://dx.doi.org/10.1186/s12884-018-1975-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157249PMC
September 2018

Prevalence of vancomycin-variable Enterococcus faecium (VVE) among vanA-positive sterile site isolates and patient factors associated with VVE bacteremia.

PLoS One 2018 22;13(3):e0193926. Epub 2018 Mar 22.

Public Health Ontario, Public Health Ontario Laboratory, Toronto, Ontario, Canada.

Vancomycin-variable enterococci (VVE) are vanA-positive, vancomycin-susceptible enterococci with the ability to revert to a vancomycin-resistant phenotype on exposure to vancomycin. We sought to assess the prevalence of VVE and to determine clinical characteristics of patients infected with VVE. We prospectively collected Enterococcus faecium sterile site isolates from Toronto Invasive Bacterial Diseases Network hospitals from January 2015 to June 2016 and calculated VVE (defined as vanA-positive, vancomycin-susceptible isolates) prevalence among vanA-containing isolates. We performed chart reviews of VVE and vancomycin-resistant E. faecium (VRE) bacteremias identified from January 2012 to June 2016, and on a random sample of patients with bacteremia due to vanA/vanB-negative, vancomycin-susceptible enterococci (VSE) from January 2015 to June 2016. Clinical characteristics were compared and factors associated with mortality assessed. Because of the potential reversion from VVE to VRE, pulsed-field gel electrophoresis (PFGE) was performed for strains causing breakthrough bacteremia in order to identify relatedness among strains with different phenotypic resistance within the same patient. VVE comprised 47% (18/38) of vanA-positive isolates. The charts of 36 VRE, 25 VVE, and 79 VSE patients were reviewed. Central venous catheter associated bacteremia was more common in VVE (44%) and VRE patients (57%) than in VSE patients (28%) (P = 0.01). The Pitt bacteremia (OR 1.3, P = 0.002) and the Charlson score (OR 1.2, P = 0.008) were the only independent mortality predictors. PFGE of strains causing breakthrough bacteremia showed high within-patient clonality, irrespective of vanA-positivity or vancomycin-susceptibility. A substantial proportion of vanA-positive isolates are VVE and are therefore not detected with conventional selective culture methods. Bacteremia sources of patients with VVE are similar to those infected with VRE. We detected no association between VVE and 30-day mortality or breakthrough bacteremia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193926PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863957PMC
June 2018

An assessment of the malaria-related knowledge and practices of Tanzania's drug retailers: exploring the impact of drug store accreditation.

BMC Health Serv Res 2018 03 9;18(1):169. Epub 2018 Mar 9.

London School of Hygiene and Tropical Medicine, London, UK.

Background: Since 2003 Tanzania has upgraded its approximately 7000 drug stores to Accredited Drug Dispensing Outlets (ADDOs), involving dispenser training, introduction of record keeping and enhanced regulation. Prior to accreditation, drug stores could officially stock over-the-counter medicines only, though many stocked prescription-only antimalarials. ADDOs are permitted to stock 49 prescription-only medicines, including artemisinin combination therapies and one form of quinine injectable. Oral artemisinin monotherapies and other injectables were not permitted at any time. By late 2011 conversion was complete in 14 of 21 regions. We explored variation in malaria-related knowledge and practices of drug retailers in ADDO and non-ADDO regions.

Methods: Data were collected as part of the Independent Evaluation of the Affordable Medicines Facility - malaria (AMFm), involving a nationally representative survey of antimalarial retailers in October-December 2011. We randomly selected 49 wards and interviewed all drug stores stocking antimalarials. We compare ADDO and non-ADDO regions, excluding the largest city, Dar es Salaam, due to the unique characteristics of its market.

Results: Interviews were conducted in 133 drug stores in ADDO regions and 119 in non-ADDO regions. Staff qualifications were very similar in both areas. There was no significant difference in the availability of the first line antimalarial (68.9% in ADDO regions and 65.2% in non-ADDO regions); both areas had over 98% availability of non-artemisinin therapies and below 3.0% of artemisinin monotherapies. Staff in ADDO regions had better knowledge of the first line antimalarial than non-ADDO regions (99.5% and 91.5%, p = 0.001). There was weak evidence of a lower price and higher market share of the first line antimalarial in ADDO regions. Drug stores in ADDO regions were more likely to stock ADDO-certified injectables than those in non-ADDO regions (23.0% and 3.9%, p = 0.005).

Conclusions: ADDO conversion is frequently cited as a model for improving retail sector drug provision. Drug stores in ADDO regions performed better on some indicators, possibly indicating some small benefits from ADDO conversion, but also weaknesses in ADDO regulation and high staff turnover. More evidence is needed on the value-added and value for money of the ADDO roll out to inform retail policy in Tanzania and elsewhere.
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http://dx.doi.org/10.1186/s12913-018-2966-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845369PMC
March 2018

Linking data sources for measurement of effective coverage in maternal and newborn health: what do we learn from individual- vs ecological-linking methods?

J Glob Health 2018 Jun;8(1):010601

Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Background: Improving maternal and newborn health requires improvements in the quality of facility-based care. This is challenging to measure: routine data may be unreliable; respondents in population surveys may be unable to accurately report on quality indicators; and facility assessments lack population level denominators. We explored methods for linking access to skilled birth attendance (SBA) from household surveys to data on provision of care from facility surveys with the aim of estimating population level effective coverage reflecting access to quality care.

Methods: We used data from Mayuge District, Uganda. Data from household surveys on access to SBA were linked to health facility assessment census data on readiness to provide basic emergency obstetric and newborn care (BEmONC) in the same district. One individual- and two ecological-linking methods were applied. All methods used household survey reports on where care at birth was accessed. The individual-linking method linked this to data about facility readiness from the specific facility where each woman delivered. The first ecological-linking approach used a district-wide mean estimate of facility readiness. The second used an estimate of facility readiness adjusted by level of health facility accessed. Absolute differences between estimates derived from the different linking methods were calculated, and agreement examined using Lin's concordance correlation coefficient.

Results: A total of 1177 women resident in Mayuge reported a birth during 2012-13. Of these, 664 took place in facilities within Mayuge, and were eligible for linking to the census of the district's 38 facilities. 55% were assisted by a SBA in a facility. Using the individual-linking method, effective coverage of births that took place with an SBA in a facility ready to provide BEmONC was just 10% (95% confidence interval CI 3-17). The absolute difference between the individual- and ecological-level linking method adjusting for facility level was one percentage point (11%), and tests suggested good agreement. The ecological method using the district-wide estimate demonstrated poor agreement.

Conclusions: The proportion of women accessing appropriately equipped facilities for care at birth is far lower than the coverage of facility delivery. To realise the life-saving potential of health services, countries need evidence to inform actions that address gaps in the provision of quality care. Linking household and facility-based information provides a simple but innovative method for estimating quality of care at the population level. These encouraging findings suggest that linking data sets can result in meaningful evidence even when the exact location of care seeking is not known.
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http://dx.doi.org/10.7189/jogh.08.010601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823029PMC
June 2018

Estimates of burden and consequences of infants born small for gestational age in low and middle income countries with INTERGROWTH-21 standard: analysis of CHERG datasets.

BMJ 2017 Aug 17;358:j3677. Epub 2017 Aug 17.

Mother and Infant Research Activities (MIRA), YB Bhawan, Thapathali, Kathmandu 921, Nepal.

 To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21 birth weight standard. Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21 birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated. CHERG birth cohorts from 14 population based sites in low and middle income countries. In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%. In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (<2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700). In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558898PMC
http://dx.doi.org/10.1136/bmj.j3677DOI Listing
August 2017

Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study.

Arch Dis Child Fetal Neonatal Ed 2018 May 5;103(3):F250-F256. Epub 2017 Aug 5.

Institute for Women's Health, University College London, London, UK.

Objective: Neonatal encephalopathy (NE) is the third leading cause of child mortality. Preclinical studies suggest infection and inflammation can sensitise or precondition the newborn brain to injury. This study examined perinatal risks factor for NE in Uganda.

Design: Unmatched case-control study.

Setting: Mulago National Referral Hospital, Kampala, Uganda.

Methods: 210 term infants with NE and 409 unaffected term infants as controls were recruited over 13 months. Data were collected on preconception, antepartum and intrapartum exposures. Blood culture, species-specific bacterial real-time PCR, C reactive protein and placental histology for chorioamnionitis and funisitis identified maternal and early newborn infection and inflammation. Multivariable logistic regression examined associations with NE.

Results: Neonatal bacteraemia (adjusted OR (aOR) 8.67 (95% CI 1.51 to 49.74), n=315) and histological funisitis (aOR 11.80 (95% CI 2.19 to 63.45), n=162) but not chorioamnionitis (aOR 3.20 (95% CI 0.66 to 15.52), n=162) were independent risk factors for NE. Among encephalopathic infants, neonatal case fatality was not significantly higher when exposed to early neonatal bacteraemia (OR 1.65 (95% CI 0.62 to 4.39), n=208). Intrapartum antibiotic use did not improve neonatal survival (p=0.826). After regression analysis, other identified perinatal risk factors (n=619) included hypertension in pregnancy (aOR 3.77), male infant (aOR 2.51), non-cephalic presentation (aOR 5.74), lack of fetal monitoring (aOR 2.75), augmentation (aOR 2.23), obstructed labour (aOR 3.8) and an acute intrapartum event (aOR 8.74).

Conclusions: Perinatal infection and inflammation are independent risk factors for NE in this low-resource setting, supporting a role in the aetiological pathway of term brain injury. Intrapartum antibiotic administration did not mitigate against adverse outcomes. The importance of intrapartum risk factors in this sub-Saharan African setting is highlighted.
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http://dx.doi.org/10.1136/archdischild-2017-312744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916101PMC
May 2018

Use of malaria rapid diagnostic tests by community health workers in Afghanistan: cluster randomised trial.

BMC Med 2017 07 7;15(1):124. Epub 2017 Jul 7.

London School of Hygiene & Tropical Medicine, London, WC1H 7HT, UK.

Background: The World Health Organisation (WHO) recommends parasitological diagnosis of malaria before treatment, but use of malaria rapid diagnostic tests (mRDTs) by community health workers (CHWs) has not been fully tested within health services in south and central Asia. mRDTs could allow CHWs to diagnose malaria accurately, improving treatment of febrile illness.

Methods: A cluster randomised trial in community health services was undertaken in Afghanistan. The primary outcome was the proportion of suspected malaria cases correctly treated for polymerase chain reaction (PCR)-confirmed malaria and PCR negative cases receiving no antimalarial drugs measured at the level of the patient. CHWs from 22 clusters (clinics) received standard training on clinical diagnosis and treatment of malaria; 11 clusters randomised to the intervention arm received additional training and were provided with mRDTs. CHWs enrolled cases of suspected malaria, and the mRDT results and treatments were compared to blind-read PCR diagnosis.

Results: In total, 256 CHWs enrolled 2400 patients with 2154 (89.8%) evaluated. In the intervention arm, 75.3% (828/1099) were treated appropriately vs. 17.5% (185/1055) in the control arm (cluster adjusted risk ratio: 3.72, 95% confidence interval 2.40-5.77; p < 0.001). In the control arm, 85.9% (164/191) with confirmed Plasmodium vivax received chloroquine compared to 45.1% (70/155) in the intervention arm (p < 0.001). Overuse of chloroquine in the control arm resulted in 87.6% (813/928) of those with no malaria (PCR negative) being treated vs. 10.0% (95/947) in the intervention arm, p < 0.001. In the intervention arm, 71.4% (30/42) of patients with P. falciparum did not receive artemisinin-based combination therapy, partly because operational sensitivity of the RDTs was low (53.2%, 38.1-67.9). There was high concordance between recorded RDT result and CHW prescription decisions: 826/950 (87.0%) with a negative test were not prescribed an antimalarial. Co-trimoxazole was prescribed to 62.7% of malaria negative patients in the intervention arm and 15.0% in the control arm.

Conclusions: While introducing mRDT reduced overuse of antimalarials, this action came with risks that need to be considered before use at scale: an appreciable proportion of malaria cases will be missed by those using current mRDTs. Higher sensitivity tests could be used to detect all cases. Overtreatment with antimalarial drugs in the control arm was replaced with increased antibiotic prescription in the intervention arm, resulting in a probable overuse of antibiotics.

Trial Registration: ClinicalTrials.gov, NCT01403350 . Prospectively registered.
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http://dx.doi.org/10.1186/s12916-017-0891-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501368PMC
July 2017

Enterobacter cloacae Complex Isolates Harboring or -Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids.

Antimicrob Agents Chemother 2017 05 24;61(5). Epub 2017 Apr 24.

National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada

Carbapenem-resistant complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A or -type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and gene analysis. The genes were found in various complex species; however, was highly associated with Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A ( = 10), IMI-1 ( = 5), and IMI-9 ( = 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, and , were harbored on different IncFII-type plasmids. complex isolates harboring -type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential.
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http://dx.doi.org/10.1128/AAC.02578-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404547PMC
May 2017

Community- and Healthcare-Associated Methicillin-Resistant Staphylococcus aureus Strains: An Investigation Into Household Transmission, Risk Factors, and Environmental Contamination.

Infect Control Hosp Epidemiol 2017 01 8;38(1):61-67. Epub 2016 Nov 8.

1Infection Prevention and Control,North York General Hospital,Toronto,Canada.

OBJECTIVE To measure transmission frequencies and risk factors for household acquisition of community-associated and healthcare-associated (HA-) methicillin-resistant Staphylococcus aureus (MRSA). DESIGN Prospective cohort study from October 4, 2008, through December 3, 2012. SETTING Seven acute care hospitals in or near Toronto, Canada. PARTICIPANTS Total of 99 MRSA-colonized or MRSA-infected case patients and 183 household contacts. METHODS Baseline interviews were conducted, and surveillance cultures were collected monthly for 3 months from household members, pets, and 8 prespecified high-use environmental locations. Isolates underwent pulsed-field gel electrophoresis and staphylococcal cassette chromosome mec typing. RESULTS Overall, of 183 household contacts 89 (49%) were MRSA colonized, with 56 (31%) detected at baseline. MRSA transmission from index case to contacts negative at baseline occurred in 27 (40%) of 68 followed-up households. Strains were identical within households. The transmission risk for HA-MRSA was 39% compared with 40% (P=.95) for community-associated MRSA. HA-MRSA index cases were more likely to be older and not practice infection control measures (P=.002-.03). Household acquisition risk factors included requiring assistance and sharing bath towels (P=.001-.03). Environmental contamination was identified in 78 (79%) of 99 households and was more common in HA-MRSA households. CONCLUSION Household transmission of community-associated and HA-MRSA strains was common and the difference in transmission risk was not statistically significant. Infect Control Hosp Epidemiol 2016;1-7.
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http://dx.doi.org/10.1017/ice.2016.245DOI Listing
January 2017

Building malaria out: improving health in the home.

Malar J 2016 06 15;15:320. Epub 2016 Jun 15.

Department of Disease Control, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Malaria prevalence has halved in endemic Africa since 2000, largely driven by the concerted international control effort. To achieve the new global targets for malaria control and elimination by 2030, and to sustain elimination once achieved, additional vector control interventions are urgently needed to supplement long-lasting insecticide-treated nets and indoor residual spraying, which both rely on effective insecticides for optimal protection. Improving housing and the built environment is a promising strategy to address this need, with an expanding body of evidence that simple modifications to reduce house entry by malaria vectors, such as closing eaves and screening doors and windows, can help protect residents from malaria. However, numerous questions remain unanswered, from basic science relating to the optimal design of house improvements through to their translation into operational use. The Malaria Journal thematic series on 'housing and malaria' collates articles that contribute to the evidence base on approaches for improving housing to reduce domestic malaria transmission.
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http://dx.doi.org/10.1186/s12936-016-1349-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910219PMC
June 2016

The Impact of an Intervention to Improve Malaria Care in Public Health Centers on Health Indicators of Children in Tororo, Uganda (PRIME): A Cluster-Randomized Trial.

Am J Trop Med Hyg 2016 Aug 6;95(2):358-367. Epub 2016 Jun 6.

Department of Clinical Research, Department of Medical Statistics, Department of Infectious Disease Epidemiology, Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Optimizing quality of care for malaria and other febrile illnesses is a complex challenge of major public health importance. To evaluate the impact of an intervention aiming to improve malaria case management on the health of community children, a cluster-randomized trial was conducted from 2010-2013 in Tororo, Uganda, where malaria transmission is high. Twenty public health centers were included; 10 were randomized in a 1:1 ratio to intervention or control. Households within 2 km of health centers provided the sampling frame for the evaluation. The PRIME intervention included training in fever case management using malaria rapid diagnostic tests (mRDTs), patient-centered services, and health center management; plus provision of mRDTs and artemether-lumefantrine. Cross-sectional community surveys were conducted at baseline and endline (N = 8,766), and a cohort of children was followed for approximately 18 months (N = 992). The primary outcome was prevalence of anemia (hemoglobin < 11.0 g/dL) in children under 5 years of age in the final community survey. The intervention was delivered successfully; however, no differences in prevalence of anemia or parasitemia were observed between the study arms in the final community survey or the cohort. In the final survey, prevalence of anemia in children under 5 years of age was 62.5% in the intervention versus 63.1% in control (adjusted risk ratio = 1.01; 95% confidence interval = 0.91-1.13; P = 0.82). The PRIME intervention, focusing on training and commodities, did not produce the expected health benefits in community children in Tororo. This challenges common assumptions that improving quality of care and access to malaria diagnostics will yield health gains.
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http://dx.doi.org/10.4269/ajtmh.16-0103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973182PMC
August 2016

Measuring implementation strength: lessons from the evaluation of public health strategies in low- and middle-income settings.

Health Policy Plan 2016 Sep 9;31(7):860-7. Epub 2016 Mar 9.

Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Evaluation of strategies to ensure evidence-based, low-cost interventions reach those in need is critical. One approach is to measure the strength, or intensity, with which packages of interventions are delivered, in order to explore the association between implementation strength and public health gains. A recent systematic review suggested methodological guidance was needed. We described the approaches used in three examples of measures of implementation strength in evaluation. These addressed important public health topics with a substantial disease burden in low-and middle-income countries; they involved large-scale implementation; and featured evaluation designs without comparison areas. Strengths and weaknesses of the approaches were discussed. In the evaluation of Ethiopia's Health Extension Programme, implementation strength scoring for each kebele (ward) was based on aggregated data from interviews with mothers of children aged 12-23 months, reflecting their reports of contact with four elements of the programme. An evaluation of the Avahan HIV prevention programme in India used the cumulative amount of Avahan funding per HIV-infected person spent each year in each district. In these cases, a single measure was developed and the association with hypothesised programme outcomes presented. In the evaluation of the Affordable Medicines Facility-malaria, several implementation strength measures were developed based on the duration of activity of the programme and the level of implementation of supporting interventions. Measuring the strength of programme implementation and assessing its association with outcomes is a promising approach to strengthen pragmatic impact evaluation. Five key aspects of developing an implementation strength measure are to: (a) develop a logic model; (b) identify aspects of implementation to be assessed; (c) design and implement data collection from a range of data sources; (d) decide whether and how to combine data into a single measure; and, (e) plan whether and how to use the measure(s) in outcome analysis.
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http://dx.doi.org/10.1093/heapol/czw001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977426PMC
September 2016

New Delhi metallo-β-lactamase in Jamaica.

J Infect Dev Ctries 2016 Feb 28;10(2):183-7. Epub 2016 Feb 28.

University of West Indies, Kingston, Jamaica.

Introduction: The global dissemination of the New Delhi metallo-beta-lactamase (NDM) gene among certain strains of bacteria has serious implications since the infections caused by such organisms pose a therapeutic challenge. Although the NDM gene has been detected in various parts of the world, this is the first report of its detection in the English-speaking Caribbean. The NDM producing Klebsiella pneumoniae was isolated from an Indian patient who had recently relocated to Jamaica.

Methodology: Identification and susceptibility testing of the K. pneumoniae isolate was performed using the Vitek 2 automated system) in keeping with Clinical and Laboratory Standards Institute (CLSI) standards. It was identified as a metallobetalactamase producer using the Rosco KPC+MBL kit. Genotypic screening for common betalactamase (including carbapenemase) genes, was carried out  using two multiplex PCRs: one for SHV-, TEM-, CTX-M-, OXA-1-, and CMY-2-types, and one for VIM-, KPC-, IMP-, OXA-48, GES-, and NDM-types. Strain typing was conducted by pulsed-field gel electrophoresis (PFGE) using XbaI and multi-locus sequencing (MLS). Plasmid isolation and analysis was also performed.

Results: K. pneumoniae (N11-02395), not previously associated with the dissemination of the NDM in India, Sweden or the UK, was found to harbor the NDM-1 gene on plasmid pNDM112395.

Conclusion: The identification of the NDM-1 gene underscores the need for effective surveillance and infection control measures to identify and prevent spread of multidrug resistant Gram negative bacilli. Strict infection control measures implemented for this patient helped to prevent the spread of this organism to other patients.
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http://dx.doi.org/10.3855/jidc.7094DOI Listing
February 2016

The Affordable Medicines Facility-malaria (AMFm): are remote areas benefiting from the intervention?

Malar J 2015 Oct 9;14:398. Epub 2015 Oct 9.

Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK.

Background: To assess the availability, price and market share of quality-assured artemisinin-based combination therapy (QAACT) in remote areas (RAs) compared with non-remote areas (nRAs) in Kenya and Ghana at end-line of the Affordable Medicines Facility-malaria (AMFm) intervention.

Methods: Areas were classified by remoteness using a composite index computed from estimated travel times to three levels of service centres. The index was used to five categories of remoteness, which were then grouped into two categories of remote and non-remote areas. The number of public or private outlets with the potential to sell or distribute anti-malarial medicines, screened in nRAs and RAs, respectively, was 501 and 194 in Ghana and 9980 and 2353 in Kenya. The analysis compares RAs with nRAs in terms of availability, price and market share of QAACT in each country.

Results: QAACT were similarly available in RAs as nRAs in Ghana and Kenya. In both countries, there was no statistical difference in availability of QAACT with AMFm logo between RAs and nRAs in public health facilities (PHFs), while private-for-profit (PFP) outlets had lower availability in RA than in nRAs (Ghana: 66.0 vs 82.2 %, p < 0.0001; Kenya: 44.9 vs 63.5 %, p = <0.0001. The median price of QAACT with AMFm logo for PFP outlets in RAs (USD1.25 in Ghana and USD0.69 in Kenya) was above the recommended retail price in Ghana (US$0.95) and Kenya (US$0.46), and much higher than in nRAs for both countries. QAACT with AMFm logo represented the majority of QAACT in RAs and nRAs in Kenya and Ghana. In the PFP sector in Ghana, the market share for QAACT with AMFm logo was significantly higher in RAs than in nRAs (75.6 vs 51.4 %, p < 0.0001). In contrast, in similar outlets in Kenya, the market share of QAACT with AMFm logo was significantly lower in RAs than in nRAs (39.4 vs 65.1 %, p < 0.0001).

Conclusion: The findings indicate the AMFm programme contributed to making QAACT more available in RAs in these two countries. Therefore, the AMFm approach can inform other health interventions aiming at reaching hard-to-reach populations, particularly in the context of universal access to health interventions. However, further examination of the factors accounting for the deep penetration of the AMFm programme into RAs is needed to inform actions to improve the healthcare delivery system, particularly in RAs.
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http://dx.doi.org/10.1186/s12936-015-0904-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600285PMC
October 2015

Uptake, Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre, Malawi: A Community-Based Prospective Study.

PLoS Med 2015 Sep 8;12(9):e1001873. Epub 2015 Sep 8.

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; London School of Hygiene & Tropical Medicine, London, United Kingdom.

Background: Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population.

Methods And Findings: Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1-12, with adolescents (16-19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159-426). HIVST uptake in months 13-24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%-7.8%) positive participants. Being "forced to test", usually by a main partner, was reported by 2.9% (95% CI 2.6%-3.2%) of 10,017 questionnaire respondents in months 1-12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%-97.0%) and a specificity of 99.9% (95% CI 99.6%-100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover.

Conclusions: Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings.
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http://dx.doi.org/10.1371/journal.pmed.1001873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562710PMC
September 2015

The evidence for improving housing to reduce malaria: a systematic review and meta-analysis.

Malar J 2015 Jun 9;14:209. Epub 2015 Jun 9.

School of Biological and Biomedical Sciences, Durham University, Durham, DH1 3LE, UK.

Background: The global malaria burden has fallen since 2000, sometimes before large-scale vector control programmes were initiated. While long-lasting insecticide-treated nets and indoor residual spraying are highly effective interventions, this study tests the hypothesis that improved housing can reduce malaria by decreasing house entry by malaria mosquitoes.

Methods: A systematic review and meta-analysis was conducted to assess whether modern housing is associated with a lower risk of malaria than traditional housing, across all age groups and malaria-endemic settings. Six electronic databases were searched to identify intervention and observational studies published from 1 January, 1900 to 13 December, 2013, measuring the association between house design and malaria. The primary outcome measures were parasite prevalence and incidence of clinical malaria. Crude and adjusted effects were combined in fixed- and random-effects meta-analyses, with sub-group analyses for: overall house type (traditional versus modern housing); screening; main wall, roof and floor materials; eave type; ceilings and elevation.

Results: Of 15,526 studies screened, 90 were included in a qualitative synthesis and 53 reported epidemiological outcomes, included in a meta-analysis. Of these, 39 (74%) showed trends towards a lower risk of epidemiological outcomes associated with improved house features. Of studies assessing the relationship between modern housing and malaria infection (n=11) and clinical malaria (n=5), all were observational, with very low to low quality evidence. Residents of modern houses had 47% lower odds of malaria infection compared to traditional houses (adjusted odds ratio (OR) 0°53, 95% confidence intervals (CI) 0°42-0°67, p< 0°001, five studies) and a 45-65% lower odds of clinical malaria (case-control studies: adjusted OR 0°35, 95 % CI 0°20-0°62, p<0°001, one study; cohort studies: adjusted rate ratio 0°55, 95% CI 0°36-0°84, p=0°005, three studies). Evidence of a high risk of bias was found within studies.

Conclusions: Despite low quality evidence, the direction and consistency of effects indicate that housing is an important risk factor for malaria. Future research should evaluate the protective effect of specific house features and incremental housing improvements associated with socio-economic development.
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http://dx.doi.org/10.1186/s12936-015-0724-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460721PMC
June 2015

Availability and price of malaria rapid diagnostic tests in the public and private health sectors in 2011: results from 10 nationally representative cross-sectional retail surveys.

Trop Med Int Health 2015 Jun 22;20(6):744-56. Epub 2015 Mar 22.

Malaria & Child Survival Department, Population Services International, Nairobi, Kenya.

Objectives: To describe the state of the public and private malaria diagnostics market shortly after WHO updated its guidelines for testing all suspected malaria cases prior to treatment.

Methods: Ten nationally representative cross-sectional cluster surveys were conducted in 2011 among public and private health facilities, community health workers and retail outlets (pharmacies and drug shops) in nine countries (Tanzania mainland and Zanzibar surveyed separately). Eligible outlets had antimalarials in stock on the day of interview or had stocked antimalarials in the past 3 months.

Results: Three thousand four hundred and thirty-nine rapid diagnostic test (RDT) products from 39 manufacturers were audited among 12,197 outlets interviewed. Availability was typically highest in public health facilities, although availability in these facilities varied greatly across countries, from 15% in Nigeria to >90% in Madagascar and Cambodia. Private for-profit sector availability was 46% in Cambodia, 20% in Zambia, but low in other countries. Median retail prices for RDTs in the private for-profit sector ranged from $0.00 in Madagascar to $3.13 in Zambia. The reported number of RDTs used in the 7 days before the survey in public health facilities ranged from 3 (Benin) to 50 (Zambia).

Conclusions: Eighteen months after WHO updated its case management guidelines, RDT availability remained poor in the private sector in sub-Saharan Africa. Given the ongoing importance of the private sector as a source of fever treatment, the goal of universal diagnosis will not be achievable under current circumstances. These results constitute national baselines against which progress in scaling-up diagnostic tests can be assessed.
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http://dx.doi.org/10.1111/tmi.12491DOI Listing
June 2015

Vancomycin-variable enterococci can give rise to constitutive resistance during antibiotic therapy.

Antimicrob Agents Chemother 2015 Mar 15;59(3):1405-10. Epub 2014 Dec 15.

M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences and the Department of Chemistry, McMaster University, Hamilton, Ontario, Canada

Vancomycin-resistant enterococci (VRE) are notorious clinical pathogens restricting the use of glycopeptide antibiotics in the clinic setting. Routine surveillance to detect VRE isolated from patients relies on PCR bioassays and chromogenic agar-based test methods. In recent years, we and others have reported the emergence of enterococcal strains harboring a "silent" copy of vancomycin resistance genes that confer a vancomycin-susceptible phenotype (vancomycin-susceptible enterococci [VSE]) and thus escape detection using drug sensitivity screening tests. Alarmingly, these strains are able to convert to a resistance phenotype (VSE→VRE) during antibiotic treatment, severely compromising the success of therapy. Such strains have been termed vancomycin-variable enterococci (VVE). We have investigated the molecular mechanisms leading to the restoration of resistance in VVE isolates through the whole-genome sequencing of resistant isolates, measurement of resistance gene expression, and quantification of the accumulation of drug-resistant peptidoglycan precursors. The results demonstrate that VVE strains can revert to a VRE phenotype through the constitutive expression of the vancomycin resistance cassette. This is accomplished through a variety of changes in the DNA region upstream of the resistance genes that includes both a deletion of a likely transcription inhibitory secondary structure and the introduction of a new unregulated promoter. The VSE→VRE transition of VVE can occur in patients during the course of antibiotic therapy, resulting in treatment failure. These VVE strains therefore pose a new challenge to the current regimen of diagnostic tests used for VRE detection in the clinic setting.
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http://dx.doi.org/10.1128/AAC.04490-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325790PMC
March 2015

The contribution of unimproved water and toilet facilities to pregnancy-related mortality in Afghanistan: analysis of the Afghan Mortality Survey.

Trop Med Int Health 2014 Dec 20;19(12):1488-99. Epub 2014 Oct 20.

Department of Epidemiology and Population Health, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Objective: To estimate the effect of unimproved household water and toilet facilities on pregnancy-related mortality in Afghanistan.

Methods: The data source was a population-based cross-sectional study, the Afghan Mortality Survey 2010. Descriptive, univariate and multivariate logistic regression analyses were carried out, comparing 69 pregnancy-related deaths (cases) and 15386 surviving women (non-cases) who had a live birth or stillbirth between 2007 and 2010.

Results: After adjusting for confounders, households with unimproved water access had 1.91 the odds of pregnancy-related mortality [95% confidence interval (CI) 1.11-3.30] compared to households with improved water access. We also found an association between unimproved toilet facilities and pregnancy-related mortality (OR = 2.25; 95% CI 0.71-7.19; P-value = 0.169), but it was not statistically significant.

Conclusions: Unimproved household water access was an important risk factor for pregnancy-related mortality in Afghanistan. However, we were unable to discern whether unimproved water source is a marker of unhygienic environments or socio-economic position. There was weak evidence for the association between unimproved toilet facilities and pregnancy-related mortality; this association requires confirmation from larger studies.
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http://dx.doi.org/10.1111/tmi.12394DOI Listing
December 2014

Improving access to malaria medicine through private-sector subsidies in seven African countries.

Health Aff (Millwood) 2014 Sep;33(9):1576-85

Catherine Goodman is a senior lecturer in health economics and policy at the London School of Hygiene and Tropical Medicine.

Improving access to quality-assured artemisinin combination therapies (ACTs) is an important component of malaria control in low- and middle-income countries. In 2010 the Global Fund to Fight AIDS, Tuberculosis, and Malaria launched the Affordable Medicines Facility--malaria (AMFm) program in seven African countries. The goal of the program was to decrease malaria morbidity and delay drug resistance by increasing the use of ACTs, primarily through subsidies intended to reduce costs. We collected data on price and retail markups on antimalarial medicines from 19,625 private for-profit retail outlets before and 6-15 months after the program's implementation. We found that in six of the AMFm pilot programs, prices for quality-assured ACTs decreased by US$1.28-$4.34, and absolute retail markups on these therapies decreased by US$0.31-$1.03. Prices and markups on other classes of antimalarials also changed during the evaluation period, but not to the same extent. In all but two of the pilot programs, we found evidence that prices could fall further without suppliers' losing money. Thus, concerns may be warranted that wholesalers and retailers are capturing subsidies instead of passing them on to consumers. These findings demonstrate that supranational subsidies can dramatically reduce retail prices of health commodities and that recommended retail prices communicated to a wide audience may be an effective mechanism for controlling the market power of private-sector antimalarial retailers and wholesalers.
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http://dx.doi.org/10.1377/hlthaff.2014.0104DOI Listing
September 2014

National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010.

Lancet Glob Health 2013 Jul 25;1(1):e26-36. Epub 2013 Jun 25.

Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.

Background: National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010.

Methods: Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses.

Findings: In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm-SGA. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh.

Interpretation: The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases.

Funding: Bill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group (CHERG).
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http://dx.doi.org/10.1016/S2214-109X(13)70006-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221634PMC
July 2013

Community health workers and stand-alone or integrated case management of malaria: a systematic literature review.

Am J Trop Med Hyg 2014 Sep 23;91(3):461-470. Epub 2014 Jun 23.

A systematic literature review was conducted to assess the effectiveness of strategies to improve community case management (CCM) of malaria. Forty-three studies were included; most (38) reported indicators of community health worker (CHW) performance, 14 reported on malaria CCM integrated with other child health interventions, 16 reported on health system capacity, and 13 reported on referral. The CHWs are able to provide good quality malaria care, including performing procedures such as rapid diagnostic tests. Appropriate training, clear guidelines, and regular supportive supervision are important facilitating factors. Crucial to sustainable success of CHW programs is strengthening health system capacity to support commodity supply, supervision, and appropriate treatment of referred cases. The little evidence available on referral from community to health facility level suggests that this is an area that needs priority attention. The studies of integrated CCM suggest that additional tasks do not reduce the quality of malaria CCM provided sufficient training and supervision is maintained.
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http://dx.doi.org/10.4269/ajtmh.14-0094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155545PMC
September 2014

Prevalence of bloodstream pathogens is higher in neonatal encephalopathy cases vs. controls using a novel panel of real-time PCR assays.

PLoS One 2014 16;9(5):e97259. Epub 2014 May 16.

Institute for Child Health, University College London, London, United Kingdom; Department of Microbiology, Virology and Infection Control, Great Ormond Street Hospital for Children, London, United Kingdom.

Background: In neonatal encephalopathy (NE), infectious co-morbidity is difficult to diagnose accurately, but may increase the vulnerability of the developing brain to hypoxia-ischemia. We developed a novel panel of species-specific real-time PCR assays to identify bloodstream pathogens amongst newborns with and without NE in Uganda.

Methodology: Multiplex real-time PCR assays for important neonatal bloodstream pathogens (gram positive and gram negative bacteria, cytomegalovirus (CMV), herpes simplex virus(HSV) and P. falciparum) were performed on whole blood taken from 202 encephalopathic and 101 control infants. Automated blood culture (BACTEC) was performed for all cases and unwell controls.

Principal Findings: Prevalence of pathogenic bacterial species amongst infants with NE was 3.6%, 6.9% and 8.9%, with culture, PCR and both tests in combination, respectively. More encephalopathic infants than controls had pathogenic bacterial species detected (8.9%vs2.0%, p = 0.028) using culture and PCR in combination. PCR detected bacteremia in 11 culture negative encephalopathic infants (3 Group B Streptococcus, 1 Group A Streptococcus, 1 Staphylococcus aureus and 6 Enterobacteriacae). Coagulase negative staphylococcus, frequently detected by PCR amongst case and control infants, was considered a contaminant. Prevalence of CMV, HSV and malaria amongst cases was low (1.5%, 0.5% and 0.5%, respectively).

Conclusion/significance: This real-time PCR panel detected more bacteremia than culture alone and provides a novel tool for detection of neonatal bloodstream pathogens that may be applied across a range of clinical situations and settings. Significantly more encephalopathic infants than controls had pathogenic bacterial species detected suggesting that infection may be an important risk factor for NE in this setting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097259PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023955PMC
January 2015
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