African Journal of
Microbiology Research

  • Abbreviation: Afr. J. Microbiol. Res.
  • Language: English
  • ISSN: 1996-0808
  • DOI: 10.5897/AJMR
  • Start Year: 2007
  • Published Articles: 5181

Review

Value of matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry in clinical microbiology and infectious diseases in Africa and tropical areas

Cheikh Ibrahima Lo
  • Cheikh Ibrahima Lo
  • Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
  • Google Scholar
Bécaye Fall
  • Bécaye Fall
  • Hôpital Principal de Dakar, Senegal.
  • Google Scholar
Bissoume Sambe-Ba
  • Bissoume Sambe-Ba
  • Hôpital Principal de Dakar, Senegal.
  • Google Scholar
Christophe Flaudrops
  • Christophe Flaudrops
  • Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
  • Google Scholar
Ngor Faye
  • Ngor Faye
  • Laboratory of General Parasitology, Cheikh Anta Diop University, Dakar, Senegal.
  • Google Scholar
Oleg Mediannikov
  • Oleg Mediannikov
  • Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
  • Google Scholar
Cheikh Sokhna
  • Cheikh Sokhna
  • Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
  • Google Scholar
Boubacar Wade
  • Boubacar Wade
  • Hôpital Principal de Dakar, Senegal.
  • Google Scholar
Didier Raoult
  • Didier Raoult
  • Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
  • Google Scholar
Florence Fenollar
  • Florence Fenollar
  • Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
  • Google Scholar


  •  Received: 24 June 2017
  •  Accepted: 11 September 2017
  •  Published: 21 September 2017

 ABSTRACT

Matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MALDI-TOF MS) is a revolutionary technique with multiple applications. Its use in clinical microbiology is now becoming widespread as the method is an easy, rapid, effective, accurate, and cheap way to identify cultured bacteria and fungi. It is, therefore, an ideal tool to replace conventional methods still used in Africa and tropical areas for routine microbiological diagnosis. The recent installation of a MALDI-TOF MS for diagnostic purposes in a hospital in Senegal has confirmed that this tool is not only valuable but also robust in tropical Africa, providing further evidence that this technique should be widely distributed there. However, despite its value for clinical microbiology in Africa, the acquisition and installation of MALDI-TOF MS is subject to several constraints. This review provides general information on aspects of MALDI-TOF MS. The specific aspects and constraints observed in Africa and tropical countries are also addressed with suggestions for appropriate solutions.

Key words: Microorganism, infectious diseases, quick identification, matrix-assisted laser desorption-ionization time-of-flight, matrix assisted laser desorption ionization-time of flight (MALDI-TOF).


 INTRODUCTION

Cardiovascular diseases are the leading cause of death in developed countries, while in Africa and low-income countries, thousands of deaths linked to infectious diseases are recorded every year (Prost, 2000;  Lopez  et al., 2000; Bryce et al., 2005; Williams et al., 2002).
 
Against this backdrop of the high incidence of infectious diseases, including emerging and reemerging pathogens (Desenclos and De Valk, 2005),  improving  tools  for  the identification of microorganisms in clinical microbiology laboratories is urgently required. 
 
In African countries, routine diagnostic methods are generally based on culture media, followed by growth characteristics and biochemical patterns. These steps are fastidious, requiring large quantities of expensive reagents and a priori knowledge of the isolated microorganism; identification may take place after several hours or days, depending on the microorganism, and even then is sometimes inaccurate (Seng et al., 2009).
 
Recently, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has enabled a revolution in the routine work of clinical microbiology laboratories with the quick, inexpensive, and accurate identification of bacteria and fungi. Without any a priori knowledge, it is possible to quickly adapt first line anti-infective treatment as the best possible treatment (Courcol, 2009). MALDI-TOF MS is having a real impact on global health and its implementation will be of great value in Africa and other tropical areas, as recently shown in Senegal, where its broad applicability and robustness have been recently proven (Fall et al., 2015; Lo et al., 2015).
 
Here, we will review the general aspects of MALDI-TOF MS but will also focus on the specific aspects and constraints observed in Africa and tropical countries. We will also propose appropriate solutions.


 GENERAL ASPECTS OF MALDI-TOF MS TECHNOLOGY

In 1975, the scientific literature began to combine MS with pyrolysis for the detection of bacterial proteins (Intelicato-Young and Fox, 2013). In 2009, a new revolution in clinical microbiology began when the efficiency of MALDI-TOF MS for the routine identification of bacteria was demonstrated with a correct identification of 95 and 84% of the genus and species levels, respectively, for 1,660 bacteria (Seng et al., 2009; Seng et al., 2010).
 
Since then, an explosion in scientific publications on the use of MALDI-TOF MS in clinical microbiology has been observed (Figure 1), supporting the fact that the method is a fast and reliable means of identifying microorganisms and is clearly more efficient than conventional methods (Eigner et al., 2009; Blondiaux et al., 2010). It has been estimated that ten bacterial strains can be identified in parallel in less than 15 min with MS, while  it  takes  more   than   360  min   to do so using conventional automated systems (Biswas and Rolain, 2013; Cherkaoui et al., 2010).
 
 
Currently, three MALDI-TOF mass spectrometers are on the market (Figure 2); the Andromas system (Paris, France) (Bille et al., 2012), the Microflex LT (Bruker Daltonics, Heidelberg, Germany, in collaboration with Becton Dickinson, Franklin Lakes, NJ, USA) (Lee et al., 2015; Saffert et al., 2011), and the VITEK® MS (bioMérieux, Marcy l’Etoile, France) (Patel, 2013). 
 
 
For bacterial and fungal identification, one isolated colony is picked and directly deposited on a well of a MALDI-TOF plate, preferentially in duplicate, as the deposit is crucial for accurate identification (Figure 3) (Fenselau and Demirev, 2001). This preparation must then be overlaid with a matrix solution (solution with alpha-cyano-4-hydroxycinnamic acid, acetonitrile, trifluoroacetic acid, etc.), and air dried at room temperature (about five minutes) to permit co-crystallization (Shunsuke et al., 2014) before placing the plate in the MALDI-TOF instrument for analysis. Identification is achieved by comparing the spectra of analyzed species against the reference spectra present in the MALDI-TOF database (Coltella et al., 2013; Martiny et al., 2012). 
 
 
Identification robustness depends on the richness of the databases, which have been regularly and substantially updated since 2009 (Seng et al., 2010). The database provided with the Vitek MS installed in Dakar, is annually updated by bioMérieux. Indeed, commercial database are regularly updated and released (approximately one time per year). Besides, depending on the MALDI-TOF mass spectrometer, database can be incremented directly with spectra from local bacteria paving way for data with local epidemiology. Specific database can also be created for entomology (Sambou et al., 2015).
 
Recently, Tran et al. (2015) performed a huge study to evaluate the cost savings of implementing routine microbiological identification by MALDI-TOF MS (bioMérieux Vitek, Durham, NC, USA) in their laboratory.
 
Overall, reagent costs for the conventional methods averaged $3.59 per isolate, while those for MS were $0.43. The use of MS was equated to a net saving of $69,108.61 (87.8%) in reagent costs annually. When technologists’ time and maintenance costs were included, conventional identification cost would be $142,532.69 versus $68,886.51 with MS, resulting in a laboratory saving of $73,646.18 (51.7%) annually. They also estimated that the initial cost of the instrument at their usage level would be offset in about three years (Tran et al., 2015). Comparing MALDI-TOF MS to other identification methods which is usually used in microbiology laboratories shows that it is very cost-effective in terms of reagent cost and working time (Table 1) (Musser, 2014).
 
The direct identification of microorganisms in specimens such as blood cultures, urine, or cerebrospinal fluid has been proposed using home-made (Segawa et al., 2014; Ferreira et al., 2010; Yonetani et al., 2016; Foster, 2013; Ferroni et al., 2010; Ferreira et al., 2011) or commercial kits for blood cultures (Jamal et al., 2013; Haigh et al., 2013; Nonnemann et al., 2013).
 
Currently, direct identification is mainly available for blood cultures after a pre-incubation step but it allows the quick identification of the involved microorganism and the opportunity of considerably earlier  treatment  adaptation, with a direct clinical impact (Kohlmann et al., 2015).
 
In addition, MALDI-TOF MS is a promising, easy, inexpensive, and rapid tool for investigating an outbreak (Croxatto et al., 2012; Gaia et al., 2011; Fujinami et al., 2011; Williamson et al., 2008). For example, the epidemiological investigation of a nosocomial outbreak of multidrug resistant Corynebacterium striatum showed that all outbreak-related strains are clustered in a single clone with a MALDI-TOF MS dendrogram (Verroken et al., 2013). It has also enabled the accurate and reproducible discrimination of major methicillin-resistant Staphylococcus aureus (MRSA) clonal complexes observed in outbreaks, belonging to strains prepared with the same extraction protocol (Wolters et al., 2011; Josten et al., 2013).
 
MALDI-TOF MS has also made it possible to differentiate the five most frequently-isolated Salmonella enterica serovars (Enteritidis, Typhimurium, Virchow, Infantis, and Hadar) (Dieckmann and Malorny, 2011) as well as to identify Escherichia coli pathotypes (Clark et al., 2013; Barbuddhe et al., 2008). The validity of MALDI-TOF MS for typing extended-spectrum β-lactamase-producing E. coli in a previously published nosocomial outbreak was recently assessed (Egli et al., 2015). Thus, all these data clearly show that MALDI-TOF MS has a promising future in the epidemiological surveillance of infectious diseases (Doern and Butler-Wu, 2016).
 
Africa is prey to endemic diseases such as malaria. This is why the use of rapid and effective control methods could permit the prevention and control of vector-borne diseases. Several studies have shown that MALDI-TOF MS has also enabled the rapid detection of arthropod vectors, such as ticks, mosquitoes, fleas (Yssouf et al., 2014), phlebotomine sand flies (Mathis et al., 2015), and Culicoides without any expertise or skills in entomology (Sambou et al., 2015; Yssouf et al., 2013a).
 
Recently, the utility of MALDI-TOF MS for a dual identification of tick species and bacteria has been demonstrated. Intracellular Rickettsia spp. has been detected using MALDI-TOF MS in ticks (Yssouf et al., 2015), as well as Borrelia crocidurae in Ornithodoros sonrai ticks (Fotso et al., 2014). This concept offers new perspectives for monitoring other vector borne diseases that present public health concerns. 
 
 
Finally, MALDI-TOF MS has also facilitated the identification of meat origin in raw and processed meats, and fish in culinary preparations (Mazzeo et al., 2008; Flaudrops et al., 2015). Key stages in the use of MALDI-TOF MS for identification purposes other than microbial purposes are summarized in Table 2 (Yssouf et al., 2014; Yssouf et al., 2013a; Mazzeo et al., 2008; Kaufmann et al., 2012; Yssouf et al., 2013b; Steinmann et al., 2013; Flaudrops et al., 2015).
 


 VALUE OF MALDI-TOF MS IN AFRICA

Bacterial and fungal identification in Africa
 
Conventional biochemical identification methods (Figure 4) are in standard use in Africa, although performance limitations sometimes exist (Patel, 2013; Samb-Ba et al., 2014). Storage of the various reagents requires strict conditions and compliance with expiration dates. Difficulties with cold storage are also observed, which can have a real impact on reagents. Reagent supply issues have also been experienced. Finally, identification is often based on interpretation of the few biochemical tests available, sometimes leading to inaccurate identification which can have a clinical impact on patient treatment. Thus, use of new-generation technologies such as MALDI-TOF MS may resolve many of these difficulties. The low cost, speed, and accuracy of identification without prior knowledge supports the claim that  the use of  MALDI-TOF MS will help in microbiology laboratories in Africa (Cherkaoui et al., 2010; Bizzini and Greub, 2010). When we implemented a VITEK® mass spectrometer RUO (bioMérieux, Marcy l'Etoile, France) in Senegal (Hôpital Principal de Dakar) in 2012, conventional methods such as API strips were immediately stopped. In just ten months, the instrument correctly identified 2,082 bacteria and fungi at the species level (85.7%) (Fall et al., 2015).
 
 
Specific aspects and constraints for MALDI-TOF MS in Africa
 
Constraints for acquisition and installation
 
The primary obstacle in performing microbial identification using MALDI-TOF MS is the cost of the equipment, which is estimated at between $120,000 and $270,000 (Tran et al., 2015). Electricity is another constraint, as it must be supplied continuously for MS. Thus, the presence of an electric generator is required to prevent power failure. Moreover, the instrument, as well as all the connected computers, must be equipped with an inverter in case of micro-power cuts. The room in which the equipment is housed must be protected from insects and dust, and must be thermo-isolated; air conditioning is mandatory.
 
Constraints for routine microbial identification
 
The main reagent required to perform MALDI-TOF MS is the chemical matrix, which is not expensive, particularly when it is home-made (Seng et al., 2009; Martiny et al., 2014). Home-made solutions can also be freshly prepared each day in not more than 10 min and stored at room temperature for the day. None of the reagents (acetonitrile solution, water, trifluoroacetic acid solution, and α-Cyano-4-hydroxycinnamic acid) need to be frozen; α -Cyano-4-hydroxycinnamic acid is the only reagent that must be stored away from light. The chemical matrix must be stored at +4°C only when purchased matrices or home-made matrices prepared a few days before are used. Commercialized standards also need to be frozen at -20°C, but fresh E. coli cultures can also be used as standard. Thus, reagents are not a limitation to the process of microbial identification when home-made matrices are prepared on a daily basis and E. coli is freshly cultivated. Each system includes spot target plates, but the plates are reusable steel targets for the Microflex LT, while the VITEK® MS uses disposable plastic targets (Deak et al., 2015). Humans may be a constraint as staff must be previously and specifically trained in the use of MALDI-TOF MS. However, it is an easy system which does not require specific prior expertise. Moreover, the required skills are quickly acquired. For example, in Senegal, after a four-day course including theoretical and practical training, the four people who completed the training course provided by two engineers from bioMérieux were autonomous in the use of MALDI-TOF MS (Fall et al., 2015).
 
Constraints for maintenance
 
The second main obstacle to the use of MALDI-TOF MS in Africa is maintenance. Annual maintenance is recommended by the manufacturers, which raises two problems: its cost, including the cost of spare parts, labor and maintenance contracts; and the lack of trained personnel in Africa to perform it. The spare parts that need to be changed most frequently are the laser and detector (depending on frequency of use) and the primary pump (a lifespan of three to four years). Overall, for the MALDI-TOF mass spectrometer that was implanted in Senegal, when moderate problems are observed  (two  or three times per year), a web connection is established between the local instrument in Dakar and the company in France. This kind of maintenance concerns the fine tuning and the diagnostic of eventual issues. In parallel, maintenance is done once per year by moving an engineer from France.
 
Solutions
 
Funding for the acquisition and maintenance of MALDI-TOF MS in Africa is the main constraint for implementing the technology. Routine identification does not actually raise problems or limitations.
 
For this study, the cost of acquiring the apparatus in Dakar was covered and shared between several organizations, including the Institute of Research for Development, a public French organization involved in research with and for southern countries, the Mediterranean Infection Hospital-University Institute, which promotes the fight against infectious diseases on a global scale, and the French Ministry of Foreign Affairs (Fall et al., 2015; Lo et al., 2015). For others, research organizations, non-governmental organizations, or charity foundations, such as the Mérieux Foundation or the Melinda and Bill Gates Foundation, which are both already involved in the use of new tools to prevent and treat deadly diseases in Africa, could help fund this equipment.
 
Currently, the strategy applied in several countries to lower management costs involves grouping clinical microbiology laboratories into large core laboratories. Thus, the development of a common MS platform between several clinical microbiology laboratories in nearby areas would appear to be the best option to share the costs. The experience of MALDI-TOF MS networking in university hospitals in Belgium has recently been reported for identifying microorganisms in Brussels (Martiny et al., 2014).
 
Over a one-month period, 1,055 isolates were identified using conventional techniques from the first hospital and analyzed by MALDI-TOF MS in another hospital situated at 7.5 km away; target plates and identification projects were sent. Identification by the MALDI-TOF networking system was more accurate and faster than that carried out in parallel with conventional methods which led to a substantial annual cost savings (Martiny et al., 2014).
 
Twelve months ago, the study clinical microbiology laboratory (University Hospital, Marseille, France) also opened up access to MALDI-TOF MS platform for use by other hospitals: the public health hospital from Salon de Provence, a remote town 52 km away with 400 beds, and the military teaching hospital of Marseille (Laveran), a general hospital with open access for both military personnel and civilians with 303 beds (personal data). Every week, hundreds of bacteria were correctly identified at a low cost without moving patients. Thus, the use of the same MALDI-TOF MS platform enables skills to be shared and reduces the cost of acquiring and maintaining the instrument (Martiny et al., 2014).
 
The MALDI-TOF mass spectrometer, that we managed, is installed at the Hôpital Principal de Dakar (Senegal) since 2012 (Fall et al., 2015). This platform is open to other health structures as well as research centers located in Dakar and its periphery as indicated on Figure 5. The samples shipment to the platform is frequent  for  centers  like  the  Institute  of  Research   for Development (IRD) and the Pasteur Institute but it is rarer for structures such as the Le Dantec Hospital and the public center of biologic and medical analysis of the Hôpital Abass Ndao. 
 
 
Indeed, the platform becomes a real support for the identification of microorganisms isolated from patients in these structures. IRD prepares its own target plates; all the other structures send the strains they have been unable to correctly identify using conventional methods directly  to the hospital. The time  for target plate  transfer to the platform varies depending on the road traffic but it never exceeds an hour and a half. A low quality of deposit linked to transfer between sites and temperature has never been observed. When the target plates arrived at the platform, only the qualified personnel of the platform perform the plate's analysis. Interpretation of the data is also performed by the personnel of the platform, except for the plates from the IRD.
 
Indeed, qualified people and Saramis software (bioMérieux) are both available at the IRD. Thus, raw data can be retrieved and interpreted there. For other structures, interpreted data can be recuperated directly or send by email. If a MALDI-TOF MS platform is established, a cooperation agreement and a convention should be established between the various teams in order to specify not only the organization of workflows but also the tasks and responsibilities of everyone involved. Finally, local maintenance staff should be specifically trained. 


 CONCLUSION

The rapidity, efficiency, and low cost have led many laboratories to adopt the MALDI-TOF as a tool for routine diagnosis, resulting to an improvement in patient care. The first successful use of a MALDI-TOF mass spectrometer in Senegal supports the fact that it is a robust and potentially valuable tool in tropical Africa which should be widely distributed there. The development of shared MALDI-TOF MS platforms in nearby geographic areas will allow equipment, skills, and costs to be shared.


 CONFLICT OF INTERESTS

The authors have not declared any conflict of interests.



 REFERENCES

Barbuddhe SB, Maier T, Schwarz G, Kostrzewa M, Hof H, Domann E (2008). Rapid identification and typing of listeria species by matrix-assisted laser desorption ionization time of flight mass spectrometry. Appl. Environ. Microbiol.74 (17):5402-5407.
Crossref

 

Bille E, Dauphin B, Leto J, Bougnoux M-E, Beretti JL, Lotz A (2012). MALDI-TOF MS Andromas strategy for the routine identification of bacteria, mycobacteria, yeasts, Aspergillus spp. and positive blood cultures. Clin. Microbiol. Infect. 18(11):1117-25.
Crossref

 
 

Biswas S, Rolain JM (2013). Use of MALDI-TOF mass spectrometry for identification of bacteria that are difficult to culture. J. Microbiol. Methods 92(1):14-24.
Crossref

 
 

Bizzini A, Greub G (2010). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, a revolution in clinical microbial identification. Clin. Microbiol. Infect. 16(11):1614-1619.
Crossref

 
 

Blondiaux N, Gaillot O, Courcol R-J (2010). MALDI-TOF mass spectrometry to identify clinical bacterial isolates: evaluation in a teaching hospital in Lille. Pathol. Biol. 58(1):55-57.
Crossref

 
 

Bryce J, Boschi-Pinto C, Shibuya K, Black RE (2005). WHO estimates of the causes of death in children. Lancet 365(9465):1147-1152.
Crossref

 
 

Cherkaoui A, Hibbs J, Emonet S, Tangomo M, Girard M, Francois P (2010). Comparison of two matrix-assisted laser desorption ionization time-of-flight mass spectrometry methods with conventional phenotypic identification for routine identification of bacteria to the species level. J. Clin. Microbiol. 48(4):1169-1175.
Crossref

 
 

Clark CG, Kruczkiewicz P, Guan C, McCorrister SJ, Chong P, Wylie J (2013). Evaluation of MALDI-TOF mass spectroscopy methods for determination of Escherichia coli pathotypes. J. Microbiol. Methods 94(3):180-191.
Crossref

 
 

Coltella L, Mancinelli L, Onori M, Lucignano B, Menichella D, Sorge R (2013). Advancement in the routine identification of anaerobic bacteria by MALDI-TOF mass spectrometry. Eur. J. Clin. Microbiol. Infect. Dis. 32(9):1183-1192.
Crossref

 
 

Courcol R (2009). Quelles utilisations de la spectrométrie de masse de type MALDI-TOF en microbiologie médicale ? Rev. Franc. Lab. 416:61-64.
Crossref

 
 

Croxatto A, Prod'hom G, Greub G (2012). Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. FEMS. Microbiol. Rev. 36(2):380-407.
Crossref

 
 

Deak E, Charlton CL, Bobenchik AM, Miller SA, Pollett S, McHardy IH (2015). Comparison of the Vitek MS and Bruker Microflex LT MALDI-TOF MS platforms for routine identification of commonly isolated bacteria and yeast in the clinical microbiology laboratory. Diagn. Microbiol. Infect. Dis. 81(1):27-33.
Crossref

 
 

Desenclos JC, De Valk H (2005). Emergent infectious diseases: importance for public health, epidemiology, promoting factors, and prevention. Med. Mal. Infect. 35(2):49-61.
Crossref

 
 

Dieckmann R, Malorny B (2011). Rapid screening of epidemiologically important Salmonella enterica subsp. enterica serovars by whole cell matrix-assisted laser desorption ionization time of flight mass spectrometry. Appl. Environ. Microbiol. 77(12):4136-4146.
Crossref

 
 

Doern CD, Butler-Wu SM (2016). Emerging and Future Applications of Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry in the Clinical Microbiology Laboratory: A Report of the Association for Molecular Pathology. J. Mol. Diagn. 8(6):789-802.
Crossref

 
 

Egli A, Tschudin-Sutter S, Oberle M, Goldenberger D, Frei R, Widmer AF (2015). Matrix-assisted laser desorption/ionization time of flight mass-spectrometry (MALDI-TOF MS) based typing of extended-spectrum β-lactamase producing E. coli a novel tool for real-time outbreak investigation. PLoS One 10(4):e0120624.
Crossref

 
 

Eigner U, Holfelder M, Oberdorfer K, Betz-Wild U, Bertsch D, Fahr AM (2009). Performance of a matrix-assisted laser desorption ionization-time-of-flight mass spectrometry system for the identification of bacterial isolates in the clinical routine laboratory. Clin. Lab. 55(7-8):289-296.

 
 

Fall B, Lo CI, Samb-Ba B, Perrot N, Diawara S, Gueye MW (2015). The ongoing revolution of MALDI-TOF mass spectrometry for microbiology reaches tropical Africa. Am. J. Trop. Med. Hyg. 92(3):641-647.
Crossref

 
 

Fenselau C, Demirev PA (2001). Characterization of intact microorganisms by MALDI mass spectrometry. Mass. Spectrom. Rev. 20(4):157-171.
Crossref

 
 

Ferreira L, Sánchez-Juanes F, González-Avila M, Cembrero-Fuci-os D, Herrero-Hernández A, González-Buitrago JM, Mu-oz-Bellido JL (2010). Direct identification of urinary tract pathogens from urine samples by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J. Clin. Microbiol. 48(6):2110-2115.
Crossref

 
 

Ferreira L, Sánchez-Juanes F, Mu-oz-Bellido JL, González-Buitrago JM (2011). Rapid method for direct identification of bacteria in urine and blood culture samples by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: intact cell vs. extraction method. Clin. Microbiol. Infect. 17(7):1007-1012.
Crossref

 
 

Ferroni A, Suarez S, Beretti JL, Dauphin B, Bille E, Meyer J (2010). Real-time identification of bacteria and Candida species in positive blood culture broths by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. J. Clin. Microbiol. 48(5):1542-1548.
Crossref

 
 

Flaudrops C, Armstrong N, Raoult D, Chabrière E (2015). Determination of the animal origin of meat and gelatin by MALDI-TOF-MS. J. Food. Compost. Anal. 41:104-112.
Crossref

 
 

Foster AW (2013). Rapid identification of microbes in positive blood cultures by matrix-assisted laser desorption/ionisation Time of flight (MALDI-TOF) mass spectrometry (Vitek-MS-bioMérieux). J. Clin. Microbiol. 51(11):3717-3719.
Crossref

 
 

Fotso Fotso A, Mediannikov O, Diatta G, Almeras L, Flaudrops C, Parola P (2014). MALDI-TOF mass spectrometry detection of pathogens in vectors: the Borrelia crocidurae/Ornithodoros sonrai paradigm. PLoS. Negl. Trop. Dis. 8(7):e2984.
Crossref

 
 

Fujinami Y, Kikkawa HS, Kurosaki Y, Sakurada K, Yoshino M, Yasuda J (2011). Rapid discrimination of Legionella by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Microbiol. Res. 166(2):77-86.
Crossref

 
 

Gaia V, Casati S, Tonolla M (2011). Rapid identification of Legionella spp. by MALDI-TOF MS based protein mass fingerprinting. Syst. Appl. Microbiol. 34(1):40-44.
Crossref

 
 

Haigh JD, Green IM, Ball D, Eydmann M, Millar M, Wilks M (2013). Rapid identification of bacteria from bioMérieux BacT/ALERT blood culture bottles by MALDI-TOF MS. Br. J. Biomed. Sci. 70(4):149-155.
Crossref

 
 

Intelicato-Young J, Fox A (2013). Mass spectrometry and tandem mass spectrometry characterization of protein patterns, protein markers and whole proteomes for pathogenic bacteria. J. Microbiol. Methods 92(3):381-386.
Crossref

 
 

Jamal W, Saleem R, Rotimi VO (2013). Rapid identification of pathogens directly from blood culture bottles by Bruker matrix-assisted laser desorption laser ionization time-of-flight mass spectrometry versus routine methods. Diagn. Microbiol. Infect. Dis. 76(4):404-408.
Crossref

 
 

Josten M, Reif M, Szekat C, Al-Sabti N, Roemer T, Sparbier K (2013). Analysis of the matrix-assisted laser desorption ionization time of flight mass spectrum of Staphylococcus aureus identifies mutations that allow differentiation of the main clonal lineages. J. Clin. Microbiol. 51(6):1809-1817.
Crossref

 
 

Kaufmann C, Schaffner F, Ziegler D, Pflüger V, Mathis A (2012). Identification of field-caught Culicoides biting midges using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Parasitology 139(2):248-258.
Crossref

 
 

Kohlmann R, Hoffmann A, Geis G, Gatermann S (2015). MALDI-TOF mass spectrometry following short incubation on a solid medium is a valuable tool for rapid pathogen identification from positive blood cultures. Int. J. Med. Microbiol. 305(4-5):469-479.
Crossref

 
 

Lee M, Chung H-S, Moon H-W, Lee SH, Lee K (2015). Comparative evaluation of two matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems, Vitek MS and Microflex LT, for the identification of Gram-positive cocci routinely isolated in clinical microbiology laboratories. J. Microbiol. Methods 113:13-15.
Crossref

 
 

Lo CI, Fall B, Sambe-Ba B, Diawara S, Gueye MW, Mediannikov O, Sokhna C, Faye N, Diemé Y, Wade B, Raoult D, Fenollar F (2015). MALDI-TOF Mass Spectrometry: A Powerful Tool for Clinical Microbiology at Hôpital Principal de Dakar, Senegal (West Africa). 10(12):e0145889.

 
 

Lopez AD, Ahmad OB, Guillot M, Ferguson BD, Salomon JA, Murray CJL, Hill KH (2002). World Mortality in 2000: Life Tables for 191 Countries. Geneva: WHO 2002.

 
 

Martiny D, Busson L, Wybo I, El Haj RA, Dediste A, Vandenberg O (2012). Comparison of the Microflex LT and Vitek MS systems for routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. J. Clin. Microbiol. 50(4):1313-1325.
Crossref

 
 

Martiny D, Cremagnani P, Gaillard A, Miendje Deyi VY, Mascart G, Ebraert A, Attalibi S, Dediste A, Vandenberg O (2014). Feasibility of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) networking in university hospitals in Brussels. Eur. J. Clin. Microbiol. Infect.33:745-754.
Crossref

 
 

Mathis A, Depaquit J, DvoÅ™ák V, Tuten H, Ba-uls A-L, Halada P (2015). Identification of phlebotomine sand flies using one MALDI-TOF MS reference database and two mass spectrometer systems. Parasit. Vectors 8:266.
Crossref

 
 

Mazzeo MF, Giulio BD, Guerriero G, Ciarcia G, Malorni A, Russo GL (2008). Fish authentication by MALDI-TOF mass spectrometry. J. Agric. Food. Chem. 56(23):11071-11076.
Crossref

 
 

Musser KA (2014). Validation and implementation of MALDI-TOF MS in a Public Health Laboratory. https://www.aphl.org/conferences/proceedings/Documents/2014/Annual-Meeting/38%20Musser.pdf, May 26, 2017.

 
 

Nonnemann B, Tvede M, Bjarnsholt T (2013). Identification of pathogenic microorganisms directly from positive blood vials by matrix-assisted laser desorption/ionization time of flight mass spectrometry. APMIS 121(9):871-877.
Crossref

 
 

Patel R (2013). Matrix-assisted laser desorption ionization-time of flight mass spectrometry in clinical microbiology. Clin. Infect. Dis. 57(4):564-572.
Crossref

 
 

Prost A (2000). Maladies infectieuses : nouveau destin, nouveaux concepts. Espace, populations, sociétés 18(2):159 165.
Crossref

 
 

Saffert RT, Cunningham SA, Ihde SM, Jobe KE, Mandrekar J, Patel R (2011). Comparison of Bruker Biotyper matrix-assisted laser desorption ionization time-of-flight mass spectrometer to BD Phoenix automated microbiology system for identification of gram-negative bacilli. J. Clin. Microbiol. 49(3):887-892.
Crossref

 
 

Samb-Ba B, Mazenot C, Gassama-Sow A, Dubourg G, Richet H, Hugon P, Lagier JC, Raoult D, Fenollar F (2014). MALDI-TOF identification of the human Gut microbiome in people with and without diarrhea in Senegal. PLoS One 9(5):e87419.
Crossref

 
 

Sambou M, Aubadie-Ladrix M, Fenollar F, Fall B, Bassene H, Almeras L (2015). Comparison of matrix-assisted laser desorption ionization-time of flight mass spectrometry and molecular biology techniques for identification of Culicoides (Diptera: ceratopogonidae) biting midges in Senegal. J. Clin. Microbiol. 53(2):410-418.
Crossref

 
 

Segawa S, Sawai S, Murata S, Nishimura M, Beppu M, Sogawa K, Watanabe M, Satoh M, Matsutani T, Kobayashi M, Iwadate Y, Kuwabara S, Saeki N, Nomura F (2014). Direct application of MALDI-TOF mass spectrometry to cerebrospinal fluid for rapid pathogen identification in a patient with bacterial meningitis. Clin. Chim. Acta 435:59-61.
Crossref

 
 

Seng P, Drancourt M, Gouriet F, La Scola B, Fournier P-E, Rolain JM (2009). Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin. Infect. Dis. 49(4):543-551.
Crossref

 
 

Seng P, Rolain JM, Fournier PE, La Scola B, Drancourt M, Raoult D (2010). MALDI-TOF-mass spectrometry applications in clinical microbiology. Future Microbiol. 5(11):1733-1754.
Crossref

 
 

Shunsuke S, Setsu S, Shota M, Motoi N, Minako, Kazuyuki S, Masaharu W, Mamoru S, Tomoo M, Masayoshi K, Yasuo I, Satoshi K, Naokatsu S, Fumio N (2014). Direct application of MALDI-TOF mass spectrometry to cerebrospinal fluid for rapid pathogen identification in a patient with bacterial meningitis. Clin. Chim. Acta 435:59-61.
Crossref

 
 

Steinmann IC, Pflüger V, Schaffner F, Mathis A, Kaufmann C (2013). Evaluation of matrix-assisted laser desorption/ionization time of flight mass spectrometry for the identification of ceratopogonid and culicid larvae. Parasitology 140(3):318-27.
Crossref

 
 

Tran A, Alby K, Kerr A, Jones M, Gilligan PH (2015). Cost Savings Realized by Implementation of Routine Microbiological Identification by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. J. Clin. Microbiol. 53(8):2473-2479.
Crossref

 
 

Verroken A, Bauraing C, Deplano A, Bogaerts P, Huang D, Wauters G (2013). Epidemiological investigation of a nosocomial outbreak of multidrug-resistant Corynebacterium striatum at one Belgian university hospital. Clin. Microbiol. Infect. 20(1):44-50.
Crossref

 
 

Williams BG, Gouws E, Boschi-Pinto C, Bryce J, Dye C (2002). Estimates of world-wide distribution of child deaths from acute respiratory infections. Lancet Infect. Dis. 2(1):25-32.
Crossref

 
 

Williamson YM, Moura H, Woolfitt AR, Pirkle JL, Barr JR, Carvalho Mda G (2008). Differentiation of Streptococcus pneumoniae conjunctivitis outbreak isolates by matrix-assisted laser desorption ionization time of flight mass spectrometry. Appl. Environ. Microbiol. 74(19):5891-5897.
Crossref

 
 

Wolters M, Rohde H, Maier T, Belmar-Campos C, Franke G, Scherpe S (2011). MALDI-TOF MS fingerprinting allows for discrimination of major methicillin resistant Staphylococcus aureus lineages. Int. J. Med. Microbiol. 301(1):64-68.
Crossref

 
 

Yonetani S, Ohnishi H, Ohkusu K, Matsumoto T, Watanabe T (2016). Direct identification of microorganisms from positive blood cultures by MALDI-TOF MS using an in-house saponin method. Int. J. Infect. Dis. 52:37-42.
Crossref

 
 

Yssouf A, Almeras L, Terras J, Socolovschi C, Raoult D, Parola P (2015). Detection of Rickettsia spp in ticks by MALDI-TOF MS. PLoS. Negl. Trop. Dis. 9(2):e0003473.
Crossref

 
 

Yssouf A, Flaudrops C, Drali R, Kernif T, Socolovschi C, Berenger J-M (2013a). Matrix-assisted laser desorption ionization-time of flight mass spectrometry for rapid identification of tick vectors. J. Clin. Microbiol. 51(2):522-528.
Crossref

 
 

Yssouf A, Socolovschi C, Flaudrops C, Ndiath MO, Sougoufara S, Dehecq JS (2013b). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: an emerging tool for the rapid identification of mosquito vectors. PLoS One 8(8):e72380.
Crossref

 
 

Yssouf A, Socolovschi C, Leulmi H, Kernif T, Bitam I, Audoly G (2014). Identification of flea species using MALDI-TOF/MS. Comp. Immunol. Microbiol. Infect. Dis. 37(3):153-157.
Crossref

 

 




          */?>