• Clinical diagnostic evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria in an area receiving seasonal malaria chemoprevention in Niger

      Coldiron, M; Assao, B; Langendorf, C; Sayinzoga-Makombe, N; de la Tour, R; Piriou, E; Ciglenecki, I; Mumina, A; Guindo, O; Page, A-L; et al. (Springer Science and Business Media LLC, 2019-12-26)
      Background Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative. Methods A prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3–28 October, 2017) and during the low transmission season (28 January–31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season. Results In the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1–63.8) for the pLDH test and 57.4% (95% CI 51.5–63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1–71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3–95.0) for the pLDH test and 85.8% (95% CI 79.3–90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9–66.8) for the pLDH test and 61.9% (55.0–68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention. Conclusions The low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.
    • Clinical diagnostic evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria in an area receiving seasonal malaria chemoprevention in Niger.

      Coldiron, M; Assao, B; Langendorf, C; Sayinzoga-Makombe, N; Ciglenecki, I; de la Tour, R; Piriou, E; Bako, M; Mumina, A; Guindo, O; et al. (BioMed Central, 2019-12-26)
      BACKGROUND: Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative. METHODS: A prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3-28 October, 2017) and during the low transmission season (28 January-31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season. RESULTS: In the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1-63.8) for the pLDH test and 57.4% (95% CI 51.5-63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1-71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3-95.0) for the pLDH test and 85.8% (95% CI 79.3-90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9-66.8) for the pLDH test and 61.9% (55.0-68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention. CONCLUSIONS: The low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.
    • Continuing effectiveness of serogroup a meningococcal conjugate vaccine, Chad, 2013

      Gamougam, K; Daugla, D M; Toralta, J; Ngadoua, C; Fermon, F; Page, A-L; Djingarey, M H; Caugant, D A; Manigart, O; Trotter, C L; et al. (Center for Disease Control, 2015-01-01)
      In 2011, vaccination with a serogroup A meningococcal polysaccharide conjugate vaccine was implemented in 3 of 23 regions in Chad. Cases of meningitis declined dramatically in vaccinated areas, but an epidemic continued in the rest of Chad. In 2012, the remaining Chad population was vaccinated, and the epidemic was halted.
    • Diagnostic and Prognostic Value of Procalcitonin and C-Reactive Protein in Malnourished Children

      Page, A-L; de Rekeneire, N; Sayadi, S; Aberrane, S; Janssens, A-C; Dehoux, M; Baron, E (American Academy of Pediatrics, 2014-01-20)
      Early recognition of bacterial infections is crucial for their proper management, but is particularly difficult in children with severe acute malnutrition (SAM). The objectives of this study were to evaluate the accuracy of C-reactive protein (CRP) and procalcitonin (PCT) for diagnosing bacterial infections and assessing the prognosis of hospitalized children with SAM, and to determine the reliability of CRP and PCT rapid tests suitable for remote settings.
    • Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community trial

      Daugla, D M; Gami, J P; Gamougam, K; Naibei, N; Mbainadji, L; Narbé, M; Toralta, J; Kodbesse, B; Ngadoua, C; Coldiron, M E; et al. (Elsevier, 2013-09-11)
      A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic.
    • Enteric bacterial pathogens in children with diarrhea in niger: diversity and antimicrobial resistance

      Langendorf, C; Le Hello, S; Moumouni, A; Gouali, M; Mamaty, A-A; Grais, RF; Weill, F-X; Page, A-L (Public Library of Science, 2015-03-23)
      Although rotavirus is the leading cause of severe diarrhea among children in sub-Saharan Africa, better knowledge of circulating enteric pathogenic bacteria and their antimicrobial resistance is crucial for prevention and treatment strategies.
    • A Guide to Aid the Selection of Diagnostic Tests

      Kosack, C; Page, A-L; Klatserc, P (World Health Organization, 2017-06-26)
      In recent years, a wide range of diagnostic tests has become available for use in resource-constrained settings. Accordingly, a huge number of guidelines, performance evaluations and implementation reports have been produced. However, this wealth of information is unstructured and of uneven quality, which has made it difficult for endusers, such as clinics, laboratories and health ministries, to determine which test would be best for improving clinical care and patient outcomes in a specific context. This paper outlines a six-step guide to the selection and implementation of in vitro diagnostic tests based on Médecins Sans Frontières’ practical experience: (i) define the test’s purpose; (ii) review the market; (iii) ascertain regulatory approval; (iv) determine the test’s diagnostic accuracy under ideal conditions; (v) determine the test’s diagnostic accuracy in clinical practice; and (vi) monitor the test’s performance in routine use. Gaps in the information needed to complete these six steps and in regulatory systems are highlighted. Finally, ways of improving the quality of diagnostic tests are suggested, such as establishing a model list of essential diagnostics, establishing a repository of information on the design of diagnostic studies and improving quality control and postmarketing surveillance.
    • Health care seeking behavior for diarrhea in children under 5 in rural Niger: results of a cross-sectional survey.

      Page, A-L; Hustache, S; Luquero, F J; Djibo, A; Manzo, M L; Grais, RF; Epicentre, Paris, France. anne-laure.page@epicentre.msf.org (2011-05-25)
      Diarrhea remains the second leading cause of death in children under 5 years of age in sub-Saharan Africa. Health care seeking behavior for diarrhea varies by context and has important implications for developing appropriate care strategies and estimating burden of disease. The objective of this study was to determine the proportion of children under five with diarrhea who consulted at a health structure in order to identify the appropriate health care levels to set up surveillance of severe diarrheal diseases.
    • Infections in Children Admitted with Complicated Severe Acute Malnutrition in Niger

      Page, A-L; de Rekeneire, N; Sayadi, S; Aberrane, S; Janssens, A-C; Rieux, C; Djibo, A; Manuguerra, J-C; Ducou-le-Pointe, H; Grais, RF; et al. (Public Library of Science, 2013-07-17)
      Although malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger.
    • Low Resistance to First and Second Line Anti-Tuberculosis Drugs among Treatment Naive Pulmonary Tuberculosis Patients in Southwestern Uganda

      Orikiriza, P; Tibenderana, B; Siedner, M J; Mueller, Y; Byarugaba, F; Moore, C C; Evans, E E; Bonnet, M; Page, A-L; Bazira, J; et al. (Public Library of Science, 2015-02-06)
      There are limited data on region-specific drug susceptibility of tuberculosis (TB) in Uganda. We performed resistance testing on specimens collected from treatment-naive patients with pulmonary TB in Southwestern Uganda for first and second line anti-TB drugs. We sought to provide data to guide regional recommendations for empiric TB therapy.
    • Lowenstein-Jensen Selective Medium for Reducing Contamination in Mycobacterium tuberculosis Culture

      Kassaza, K; Orikiriza, P; Llosa, A; Bazira, J; Nyehangane, D; Page, A-L; Boum, Y (2014-07)
      We compared Mycobacterium tuberculosis sputum culture recovery and contamination rates between Lowenstein-Jensen medium (LJ) containing the following decontaminants and LJ alone: (i) PANTA (n = 299), (ii) Selectatab-MB (n = 299), and (iii) penicillin G (n = 234). The contamination rate for LJ alone was approximately 31%, versus 5.0% for PANTA-containing, 2% for Selectatab-containing, and 9% for penicillin-containing media (P < 0.001). M. tuberculosis isolation rates were 9.8%, 17%, 18%, and 12% for standard LJ, PANTA, Selectatab, and penicillin cultures, respectively.
    • Male Gender is independently associated with pulmonary tuberculosis among sputum and non-sputum producers people with presumptive tuberculosis in Southwestern Uganda

      Boum, Y; Atwine, D; Orikiriza, P; Assimwe, J; Page, A-L; Mwanga-Amumpaire, J; Bonnet, M (BioMed Central, 2014-12-10)
      BackgroundLittle is known about the association between gender and risk of TB infection. We sought to assess the impact of gender on TB prevalence among people with presumptive tuberculosis at a regional referral hospital in a high TB and HIV prevalence setting.MethodsWe analyzed data from two diagnostic TB studies conducted in rural, southwestern Uganda. People with presumptive tuberculosis were evaluated by chest X-ray, fluorescence microscopy, TB culture, and HIV testing. Our primary outcome of interest was TB infection, as defined by a positive TB culture. Our primary explanatory variable of interest was gender. We fit univariable and multivariable logistic regression models to investigate associations between TB infection and gender, before and after adjusting or possible confounding factors, including ability to produce sputum, age and residence.ResultsBetween April 2010 and September 2012, 863 people with presumptive tuberculosis (PWPTB) were enrolled in the two studies at Mbarara Regional Referral Hospital (MRRH) in Uganda. Among them 664 (76.9%) were able to produce sputum. X-ray was suggestive of TB for 258 (66.5%) of males and 175 (44.8%) of female (p¿<¿0.001). using microscopy 84 (20%) of males and 48 (10.9%) of females were diagnosed with TB (p¿<¿0.001) while 122 (30.3%) of males and 76 (18.4%) of females were diagnosed with TB (p¿<¿0.001) using TB culture.In multivariable logistic regression models, the odds of having TB was higher in males than females (AOR 2.2 (1.56-3.18 95%CI°, P¿<¿0.001), after adjustment for age, HIV status, ability to produce sputum, and residence.ConclusionIn Southwestern Uganda, TB prevalence is higher among male than female people with presumptive TB. The increased risk of TB among males is independent of other TB risk factors. These findings emphasize the need for gender-focused interventions aimed at reducing TB transmission.
    • Massive Increase, Spread, and Exchange of Extended Spectrum {beta}-Lactamase-Encoding Genes Among Intestinal Enterobacteriaceae in Hospitalized Children With Severe Acute Malnutrition in Niger.

      Woerther, P-L; Angebault, C; Jacquier, H; Hugede, H-C; Janssens, A-C; Sayadi, S; El Mniai, A; Armand-Lefèvre, L; Ruppé, E; Barbier, F; et al. (2011-10)
      Background. From the time of CTX-M emergence, extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have spread worldwide in community settings as well as in hospitals, particularly in developing countries. Although their dissemination appears linked to Escherichia coli intestinal carriage, precise paths of this dynamic are largely unknown. Methods. Children from a pediatric renutrition center were prospectively enrolled in a fecal carriage study. Antibiotic exposure was recorded. ESBL-E strains were isolated using selective media from fecal samples obtained at admission and, when negative, also at discharge. ESBL-encoding genes were identified, their environments and plasmids were characterized, and clonality was assessed with polymerase chain reaction-based methods and pulsed-field gel electrophoresis for E. coli and Klebsiella pneumoniae. E. coli strains were subjected to multilocus sequence typing. Results. The ESBL-E carriage rate was 31% at admission in the 55 children enrolled. All children enrolled received antibiotics during hospitalization. Among the ESBL-E-negative children, 16 were resampled at discharge, and the acquisition rate was 94%. The bla(CTX-M-15) gene was found in >90% of the carriers. Genetic environments and plasmid characterization evidenced the roles of a worldwide, previously described, multidrug-resistant region and of IncF plasmids in CTX-M-15 E. coli dissemination. Diversity of CTX-M-15-carrying genetic structures and clonality of acquired ESBL E. coli suggested horizontal genetic transfer and underlined the potential of some ST types for nosocomial cross-transmission. Conclusions. Cross-transmission and high selective pressure lead to very high acquisition of ESBL-E carriage, contributing to dissemination in the community. Strict hygiene measures as well as careful balancing of benefit-risk ratio of current antibiotic policies need to be reevaluated.
    • TSH-CHECK-1 test: diagnostic accuracy and potential application to initiating treatment for hypothyroidism in patients on anti-tuberculosis drugs.

      Kosack, C S; Page, A-L; Van Hulsteijn, L T; Lentjes, E G W M; Medecins sans Frontieres, Amsterdam, The Netherlands; Epicentre, Paris, France; Leiden University Medical Center, Leiden, The Netherlands; University Medical Center Utrecht, Utrecht, The Netherlands. (2012-03)
      Thyroid-stimulating hormone (TSH) promotes expression of thyroid hormones which are essential for metabolism, growth, and development. Second-line drugs to treat tuberculosis (TB) can cause hypothyroidism by suppressing thyroid hormone synthesis. Therefore, TSH levels are routinely measured in TB patients receiving second-line drugs, and thyroxin treatment is initiated where indicated. However, standard TSH tests are technically demanding for many low-resource settings where TB is prevalent; a simple and inexpensive test is urgently needed.
    • Use of Colorimetric Culture Methods for Detection of Mycobacterium Tuberculosis Complex Isolates from Sputum Samples in Resource-Limited Settings

      Boum, Y; Orikiriza, P; Rojas-Ponce, G; Riera-Montes, M; Atwine, D; Nansumba, M; Bazira, J; Tuyakira, E; De Beaudrap, P; Bonnet, M; et al. (2013-07)
      Despite recent advances, tuberculosis (TB) diagnosis remains imperfect in resource-limited settings due to its complexity and costs, poor sensitivity of available tests, or long times to reporting. We present a report on the use of colorimetric methods, based on the detection of mycobacterial growth using colorimetric indicators, for the detection of Mycobacterium tuberculosis in sputum specimens. We evaluated the nitrate reductase assay (NRA), a modified NRA using para-nitrobenzoic acid (PNB) (NRAp), and the resazurin tube assay using PNB (RETAp) to differentiate tuberculous and nontuberculous mycobacteria. The performances were assessed at days 18 and 28 using mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen (LJ) medium culture methods as the reference standards. We enrolled 690 adults with suspected pulmonary tuberculosis from a regional referral hospital in Uganda between March 2010 and June 2011. At day 18, the sensitivities and specificities were 84.6% and 90.0% for the NRA, 84.1% and 92.6% for the NRAp, and 71.2% and 99.3% for the RETAp, respectively. At day 28, the sensitivity of the RETAp increased to 82.6%. Among smear-negative patients with suspected TB, sensitivities at day 28 were 64.7% for the NRA, 61.3% for the NRAp, and 50% for the RETAp. Contamination rates were found to be 5.4% for the NRA and 6.7% for the RETAp, compared with 22.1% for LJ medium culture and 20.4% for MGIT culture. The median times to positivity were 10, 7, and 25 days for colorimetric methods, MGIT culture, and LJ medium culture,respectively. Whereas the low specificity of the NRA/NRAp precludes it from being used for TB diagnosis, the RETAp might provide an alternative to LJ medium culture to decrease the time to culture results in resource-poor settings.
    • Use of Vibrio cholerae Vaccine in an Outbreak in Guinea

      Luquero, F J; Grout, L; Ciglenecki, I; Sakoba, K; Traore, B; Heile, M; Diallo, A A; Itama, C; Page, A-L; Quilici, M-L; et al. (Massachusetts Medical Society, 2014-05-29)