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Papers by Laurence Borand

The Lancet Infectious Diseases

The International Journal of Tuberculosis and Lung Disease, 2018

To evaluate inter-reader agreement and diagnostic accuracy of chest radiography (CXR) in the diag... more To evaluate inter-reader agreement and diagnostic accuracy of chest radiography (CXR) in the diagnosis of tuberculosis (TB) in children with human immunodeficiency virus (HIV) infection. D E S I G N : HIV-infected children with clinically suspected TB were enrolled in a prospective study conducted in Burkina Faso, Cambodia, Cameroon and Viet Nam from April 2010 to December 2014. Three readers-a local radiologist, a paediatric pulmonologist and a paediatric radiologist-independently reviewed the CXRs. Inter-reader agreement was then assessed using the j coefficient. Diagnostic accuracy of CXR was assessed in culture-confirmed cases and controls. R E S U LT S : A total of 403 children (median age 7.3 years, interquartile range 3.5-9.7; 49.6% males) were enrolled. Inter-reader agreement was as follows: between local radiologist and paediatric pulmonologist, j ¼ 0.36 (95%CI 0.27-0.45); local radiologist and paediatric

Cold Spring Harbor perspectives in medicine, Jan 8, 2015

The post-2015 World Health Organization global tuberculosis strategy recognizes that elimination ... more The post-2015 World Health Organization global tuberculosis strategy recognizes that elimination requires a focus on reducing the pool of latently infected individuals, an estimated 30% of the global population, from which future tuberculosis cases would be generated. Tackling latent tuberculosis infection requires the identification and treatment of asymptomatic individuals to reduce the risk of progression to active disease. Diagnosis of latent tuberculosis infection is based on the detection of an immune response to Mycobacterium tuberculosis antigens using either the tuberculin skin test or interferon-γ release assays. Current treatment requires the use of antibiotics for at least 3 months. In this article, we review the current knowledge of the natural history, immunology, and pathogenesis of latent tuberculosis, describe key population groups for screening and risk assessment, discuss clinical management in terms of diagnosis and preventative treatment, and identify areas for ...

Gut Microbes, 2020

Background: Klebsiella pneumoniae (hereafter, Kp) is a major public health threat responsible for... more Background: Klebsiella pneumoniae (hereafter, Kp) is a major public health threat responsible for high levels of multidrug resistant (MDR) human infections. Besides, Kp also causes severe infections in the community, especially in Asia and Africa. Although most Kp infections are caused by endogenous intestinal carriage, little is known about the prevalence and microbiological characteristics of Kp in asymptomatic human carriage, and attached risk factors including environmental sources exposure. Methods: Here, 911 pregnant women from communities in Madagascar, Cambodia, and Senegal were screened for gut colonization by Kp. Characteristics of Kp strains (antimicrobial susceptibility, genomic diversity, virulence, and resistance genes) were defined, and associated risk factors were investigated. Results: Kp carriage rate was 55.9%, and Kp populations were highly heterogeneous (6 phylogroups, 325 sequence types, Simpson index 99.6%). One third of Kp isolates had acquired antimicrobial resistance genes. MDR-Kp (11.7% to 39.7%) and extended spectrum beta-lactamase (ESBL)-producing Kp (0.7% to 14.7%) varied among countries. Isolates with virulence genes were detected (14.5%). Environmental exposure factors including food, animal contacts, or hospitalization of household members were associated with carriage of Kp, antimicrobial resistance and hypervirulence. However, risk factors were countryspecific and Kp subpopulation-specific. Conclusion: This large-scale multicenter study uncovers the huge diversity of Kp in human gut carriage, demonstrates that antimicrobial resistance is widespread in communities of three lowincome countries, and underlines the challenges posed by Kp colonization to the control of antimicrobial resistance.

The Journal of antimicrobial chemotherapy, Feb 1, 2017

Antibiotic resistance is growing in low-income countries (LICs). Children in LICs are particularl... more Antibiotic resistance is growing in low-income countries (LICs). Children in LICs are particularly at risk. Information on antibiotic consumption is needed to control the development and spread of resistant bacteria. To measure antibiotic consumption and related factors, a community survey was undertaken in two sites in Madagascar (Antananarivo and Moramanga) and in Senegal (Guediawaye) among children under 2. Face-to-face interviews were conducted with parents or caregivers of eligible children. Regression analysis was used to determine variables associated with reported antibiotic consumption. Availability of health structures and health policies were also investigated. Population estimates for antibiotic consumption in the last 3 months were 37.2% (95% CI 33.4%-41.2%) in Guediawaye, 29.3% (95% CI 25.0%-34.1%) in Antananarivo and 24.6% (95% CI 20.6%-29.1%) in Moramanga. In all sites, the large majority of antibiotics were taken with a prescription (92.2%, 87.0% and 92.0% for Antan...

Journal of the Pediatric Infectious Diseases Society, 2021

Background There is no gold standard for tuberculosis diagnosis in children. Clinical Case Defini... more Background There is no gold standard for tuberculosis diagnosis in children. Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children were proposed by international experts in 2012 and updated in 2015. We aimed to compare the 2012 and 2015 Clinical Case Definitions in HIV-infected children with suspected tuberculosis. Methods We enrolled HIV-infected children with suspected tuberculosis in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS [Agence Nationale de Recherches sur le SIDA et les hépatites virales] 12229 PAANTHER [Pediatric Asian African Network for Tuberculosis and HIV Research] 01 Study). We classified children using the 2012 and 2015 Case Definitions considering as tuberculosis cases those with confirmed tuberculosis and those with probable and unconfirmed tuberculosis in the 2012 and the 2015 classifications, respectively. We assessed agreement between both classifications. Results Of 438 children enrolled, 197 (45.0%) children were class...

Pediatrics, 2019

BACKGROUND: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce ... more BACKGROUND: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis. METHODS: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony. RESULTS: A total of 438 children were enrolled in the st...

BMC Pediatrics, 2021

Background In high tuberculosis (TB) burden settings, there is growing evidence that TB is common... more Background In high tuberculosis (TB) burden settings, there is growing evidence that TB is common in children with pneumonia, the leading cause of death in children under 5 years worldwide. The current WHO standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. As a result, many children with TB-associated severe pneumonia are currently missed or diagnosed too late. We therefore propose a diagnostic trial to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra (Ultra) performed on nasopharyngeal aspirates (NPA) and stool samples to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples. Methods TB-Speed Pneumonia is a pragmatic stepped-wedge cluster randomized controlled trial conducted in six countries with h...

Social Science Research Network, 2021

bioRxiv, 2021

International efforts to curb antimicrobial resistance have focused on drug development and limit... more International efforts to curb antimicrobial resistance have focused on drug development and limiting unnecessary use. However, in areas where water, sanitation, and hygiene infrastructure is lacking, and where biosecurity in food-animal production is poor, pathogen-flow between humans and animals could exacerbate the emergence and spread of resistant pathogens. Here, we compared mobile resistance elements among Escherichia coli recovered from humans and meat in Cambodia, a country with substantial connectivity between humans and animals, unregulated antibiotic use, and poor environmental controls. We identified multiple resistance-encoding plasmids and a novel, blaCTX-M and qnrS1-encoding transposon that were widely dispersed in both humans and animals, a phenomenon rarely observed in high-income settings. Our findings indicate that plugging leaks at human-animal interfaces should be a critical part of addressing antimicrobial resistance in low and middle-income countries.

Objective—To investigate the impact of tuberculosis (TB)-associated immune reconstitution syndrom... more Objective—To investigate the impact of tuberculosis (TB)-associated immune reconstitution syndrome (IRIS) upon immunological recovery and the T cell compartment after initiation of TB and antiretroviral therapy (ART). Design and methods—We prospectively evaluated T cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n=154) of highly immunosuppressed HIV + patients with TB from the CAMELIA randomized clinical trial. We compared findings from patients who developed TB-IRIS to findings from patients who did not develop TB-IRIS. Data were evaluated with mixed effect linear regression, Kaplan-Meier estimates, and Wilcoxon rank sum tests, and q-values were calculated to control for multiple comparisons. Correspondence should be directed to: Anne E. Goldfeld, Program in Cellular and Molecular Medicine, Children’s Hospital Boston, 200 Longwood Ave., Boston, MA 02115, Tel.: 617-713-8778/Fax: 617-713-8788, anne.goldfeld@childrens.harvard.edu. *These authors ma...

The online version of this article can be found at:€DOI: 10.1177/1740774512470765Clin Trials 2013... more The online version of this article can be found at:€DOI: 10.1177/1740774512470765Clin Trials 2013 10: 300 originally published online 23 January 2013Brigitte Bazin, Genevieve Chene and and the [Quali-PED] ANRS 12175 Study GroupMina Hanna, Albert Minga, Paulin Fao, Laurence Borand, Assane Diouf, Jean-Marc Mben, Rita R Gad, Xavier Anglaret,

Frontiers in Immunology, 2019

Background: Human Immunodeficiency Virus 1 (HIV-1) and Mycobacterium Tuberculosis (Mtb) co-infect... more Background: Human Immunodeficiency Virus 1 (HIV-1) and Mycobacterium Tuberculosis (Mtb) co-infected patients are commonly at risk of immune reconstitution inflammatory syndrome (IRIS) when initiating antiretroviral treatment (ART). Evidence indicates that innate immunity plays a role in TB-IRIS. Here, we evaluate the phenotype of Gamma-delta (γδ) T cells and invariant Natural Killer (iNK) T cells in tuberculosis-associated IRIS. Methods: Forty-eight HIV+/TB+ patients (21 IRIS) and three control groups: HIV-/TB-(HD, n = 11), HIV+/TB-(n = 26), and HIV-/TB+ (n = 22) were studied. Samples were taken at ART initiation (week 2 of anti-tuberculosis treatment) and at the diagnosis of IRIS for HIV+/TB+; before ART for HIV+/TB-, and at week 2 of antituberculosis treatment for HIV-/TB+ patients. γδ T cells and Invariant natural killer T (iNKT) cells were analyzed by flow cytometry. Results: Before ART, IRIS, and non-IRIS patients showed a similar proportion of γδ pos T and iNKT cells. HLA-DR on γδ pos T cells and δ2 pos γδ pos T cells was significantly higher in TB-IRIS vs. non-IRIS patients and controls (p < 0.0001). NKG2D expression on γδ pos T cells and the δ2 pos γδ pos T cell subset was lower in HIV+/TB+ patients than controls. CD158a expression on γδ pos T cells was higher in TB-IRIS than non-IRIS (p = 0.02), HIV+/TB-, and HIV-/TB-patients. Conclusion: The higher activation of γδ pos T cells and the γδ2 pos γδ pos T cell subset suggests that γδ T cells may play a role in the pathogenesis of TB-IRIS.

Journal of Clinical Virology, 2018

BACKGROUND In Cambodia, access to hepatitis B surface antigen (HBsAg) screening is low for pregna... more BACKGROUND In Cambodia, access to hepatitis B surface antigen (HBsAg) screening is low for pregnant women and Hepatitis B Virus (HBV) DNA quantification is poorly accessible. OBJECTIVES To evaluate the performance of a serial algorithm using two HBV rapid diagnostic tests (RDTs), in which samples positive for HBsAg were further tested for HBeAg as a surrogate marker for HBV DNA quantification. STUDY DESIGN In 2015, we prospectively collected plasma samples from 250 pregnant women consulting for antenatal care in one hospital in Phnom Penh including 128 with a known positive HBsAg status. All specimens were tested with the SD BIOLINE HBsAg RDT and HBsAg ELISA assay. In ELISA-positive samples, HBeAg status was determined using the SD BIOLINE HBeAg RDT and HBV DNA quantification was assessed. RESULTS Sensitivity and specificity of HBsAg RDT were 99.2% (97.7-99.9) and 100% (97.0-100), respectively. Among the 128 ELISA-positive samples, 29 (23%) tested HBeAg positive and 34 (26.5%) had HBV DNA > 5.3 Log10 IU/mL. Sensitivity and specificity of HBeAg RDT in identifying viremic samples were 76.5% (62.2.0-90.7) and 96.8% (93.3-100) for HBV DNA > 5.3 Log10 IU/mL and 89.3% (77.8-100) and 96.0% (92.2-99.8) for HBV DNA > 7.3 Log10IU/mL. Among the 99 negative HBeAg RDT women, 8 had HBV DNA > 5.3 Log10 IU/mL and 7 of them harbored BCP/PC HBV mutants. CONCLUSIONS A combination of HBsAg and HBeAg RDTs could be a low-cost strategy to identify HBV-infected pregnant women at risk of perinatal transmission in a country were HBV DNA quantification is not routinely available.

Transactions of the Royal Society of Tropical Medicine and Hygiene, Jan 22, 2018

In Western settings, community-acquired pneumonia (CAP) due to Gram-negative bacilli (GNB) is rel... more In Western settings, community-acquired pneumonia (CAP) due to Gram-negative bacilli (GNB) is relatively rare. Previous studies from Asia, however, indicate a higher prevalence of GNB in CAP, but data, particularly from Southeast Asia, are limited. This is a prospective observational study of 1451 patients ≥15 y of age with CAP from two hospitals in Cambodia between 2007 and 2010. The proportion of GNB was estimated. Risk factors and clinical characteristics of CAP due to GNB were assessed using logistic regression models. The prevalence of GNB was 8.6% in all CAP patients and 15.8% among those with a valid respiratory sample. GNB infection was independently associated with diabetes, higher leucocyte count and CAP severity. Mortality was higher in patients with CAP due to GNB. We found a high proportion of GNB in a population hospitalized for CAP in Cambodia. Given the complex antimicrobial sensitivity patterns of certain GNBs and the rapid emergence of multidrug-resistant GNB, micr...

Respiratory Medicine, 2013

The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2010

The aims of this ANRS12154 open-label, single-center, multiple-dose pharmacokinetic study were to... more The aims of this ANRS12154 open-label, single-center, multiple-dose pharmacokinetic study were to characterize nevirapine pharmacokinetics in a Cambodian population of HIV-infected patients and to identify environmental and genetic factors of variability, focusing on the CYP2B6, CYP3A5, and ABCB1 (MDR1) genes. A total of 170 Cambodian HIV-infected patients were included. Nevirapine trough concentrations were measured after 18 and 36 months of starting antiretroviral treatment and in samples drawn during a dosing interval in a subset of 10 patients. All data were analyzed by nonlinear mixed-effects modeling. The effect of covariates was investigated using the population pharmacokinetic model. Patients carrying homozygous lossof-function alleles CYP3A5 6986A>G, CYP2B6 516G>T, CYP2B6 1459C>T, and ABCB1 3435C>T represent 42.4%, 9.2%, 0%, and 18% of the population, respectively. The median nevirapine trough concentrations did not differ after 18 and 36 months of treatment (5,705 ng/ml [range, <50 to 13,871] and 5,709 ng/ml [range, <50 to 15,422], respectively). Interpatient and intrapatient variabilities of nevirapine apparent clearance were 28% and 17%, respectively. CYP2B6 516G>T and creatinine clearance were found to significantly affect nevirapine apparent clearance. The estimated nevirapine apparent clearances were 2.95 liters/h, 2.62 liters/h, and 1.86 liters/h for CYP2B6 516GG, CYP2B6 516GT, and CYP2B6 516TT genotypes, respectively. The impact of creatinine clearance was small. This study demonstrates that 95% of the patients had sustained nevirapine exposure well above the 3,000-ng/ml threshold. Nevirapine clearance was shown to be affected by CYP2B6 516G>T genetic polymorphism and creatinine clearance, although this explained only part of the interpatient variability, which remains low compared to that for other antiretroviral drugs.