Burden of disease: HIV and other infectious diseases

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Burden of disease: HIV and other Infectious disease

Infectious diseases are contributing immensely to the burden of disease in society. It is very important to take the global burden of disease into consideration when conducting research that is directed to address some of the issues surrounding this problem. In the latest “Global burden of disease study” (Lozano et al. 2012) the strain that infectious diseases place on society was tremendous with approximately 9.5 million people succumbing to infectious diseases in 2010. Even though this was a decrease of 12.7% from 1990 it is still a very serious problem to take note of.
The trends in the 21st century that will contribute significantly to the large number of infectious diseases are the high mobility and interconnectedness of the world assisting in the spread of disease around the globe. This has been seen in the last few years since diseases spread much easier geographically then ever before (Heymann 2007). Combined with the infectious diseases spreading faster is also the factor of the quicker appearance of new emerging disease. In the period 1997 to 2007 approximately 40 new diseases had appeared that were not known before.
The study also reported that in a five year period (2002 – 2007) 1 100 epidemic events occurred world wide (Heymann 2007). The burden of infectious diseases can roughly be subdivided into the major infectious diseases as can be seen in Table 1.1. The increase in deaths due to AIDS is immense with an increase of 390.4 % in the last 20 years. Neglected diseases and as well as hepatitis have also shown to be on the increase at 9.2 and 46.4% respectively. Even though the other diseases and the total deaths by infectious diseases are showing a decrease it is nothing to be excited about when nearly 10 million people still die due to infectious diseases. When it comes to children the picture is also horrific (Fig. 1.1). Infectious diseases in 2010 were responsible for more than 50% of all deaths in children between the ages of 1 and 4, which totalled nearly 1 million deaths (Lozano et al. 2012). In sub-Saharan Africa it is noteworthy that out of the top five most deadliest causes of premature deaths, four are due to infectious diseases of which AIDS is the biggest contributor and lower respiratory disease also contributing significantly.

Overview of medicinal plants as therapeutics

The use of natural products for medicine has a long history that has delivered many new molecules to the medical field. Even with the huge swing in the last 25 years from natural to synthetic drug discovery and with a huge dip in funding experienced for natural product research in the period spanning 1984 to 2003 the numbers of patents for natural product-derived, small-molecules have remained quite stable and thus natural products are still an undiminishing source of new pharmaceuticals (Koehn and Carter 2005).
In the well-known study of Newmann and Cragg (2007) a huge emphasis was placed on the role of natural products in previous and current market drugs with new chemical entities discovered from natural resources contributing more then 25% when taking into account only natural and natural derived new chemical entities (NCE). It was also mentioned in this study that a specific group of NCE should not be disregarded, this group of molecules were the synthetic NCE that had a natural product- inspired pharmacophore and thus could also be seen as originating from a natural product. Natural products therefore do have an important role to play in the future of drug discovery.
The use of plants as medicine has been a practice even before 3 000 B.C. and is still being used up until today. Raskin and Ripoll (2004) emphasised in their study that since 3000 B.C. till today, medicinal plants have been documented by different nations throughout history. Some of the highlights mentioned by them were the Chinese emperor’s book on medicinal plant use in approximately 2700 B.C., the documentation of Indian Ayurvedic herbal medicine, the Greek text of popular herbal medicine of 78 A.D., the well documented use of medicinal medicine by the European monasteries from 500 to 1200 A.D., the isolation of morphine by Wilhelm Serturner in 1803 A.D. and the discovery of Taxol in 1971. This extended history of the use of medicinal plants is a good witness to the fact that plants do possess the necessary potential to produce large amounts of NCE to fight the onslaught of disease in the world.

TABLE OF CONTENTS :

Chapter Introduction
- 1.1. Background
- 1.1.1. Burden of disease: HIV and other infectious diseases
- 1.1.2. Medicinal Plants
  - 1.1.2.1. Overview of medicinal plants as therapeutics
  - 1.1.2.2. Medicinal plants as anti-HIV therapeutics
- 1.1.3. Metabolomics
  - 1.1.3.1. UPLC and LC-MS
  - 1.1.3.2. GC-MS
  - 1.1.3.3. NMR
- 1.2. Objectives
- 1.2.1. Hypothesis
- 1.3. Structure of thesis
- 1.4. References
Chapter Helichrysum species selected
- 2.1. Introduction
- 2.1.1. H. acutatum DC. (HACU)
- 2.1.2. H. alliodes Less. (HALL)
- 2.1.3. H. anomalum DC. (HANO)
- 2.1.4. H. appendiculatum (L.f.) Less (HAPP-1)
- 2.1.5. H. aureonitens Sch. Bip. (HAU-1)
- 2.1.6. H. cephaloideum DC. (HCEP)
- 2.1.7. H. chionosphaerum DC. (HCHI)
- 2.1.8. H. confertum N.E. Br. (HCON)
- 2.1.9. H. cymosum sp. cymosum D. Don. (HCCY)
- 2.1.10. H. cymosum sp. calvum Hilliard (HCCL)
- 2.1.11. H. difficle Hilliard (HDIF)
- 2.1.12. H. drakensbergense Killick (HDRA)
- 2.1.13. H. herbaceum (Andr.) Sweet (HHER)
- 2.1.14. H. melanacme DC. (HMEL)
- 2.1.15. H. miconiifolium DC. (HMIC)
- 2.1.16. H. natalitium DC. (HNAT)
- 2.1.17. H. nudifolium var. nudifolium (L.) Less (HNUN)
- 2.1.18. H. odoratissimum (L.) Sweet (HODO)
- 2.1.19. H. oreophilium Klatt (HOR-1)
- 2.1.20. H. oxyphyllum DC. (HOXY)
- 2.1.21. H. pallidum DC. (HPAL)
- 2.1.22. H. panduratum O. Hoffm. (HPAN)
- 2.1.23. H. pannosum DC. (HPANN)
- 2.1.24. H. pilosellum (L.f.) Less. (HPIL & HNUP)
- 2.1.25. H. populifolium D.C. (HPOP)
- 2.1.26. H. rugulosum Less. (HRUG-1)
- 2.1.27. H. splendidium Less. (HSPL-1)
- 2.1.28 H. subluteum Burtt Davy (HSUB)
- 2.1.29. H. sutherlandii Harv. (HSUT)
- 2.1.30. H. umbraculigerum Less. (HUMB)
- 2.1.31 H. vernum Hilliard (HVER)
- 2.1. References
Chapter Analysis of several South African Helichrysum species by means of NMR-based metabolomics in search of anti-HIV constituents
- 3.1. Introduction
- 3.2. Materials and Methods
- 3.2.1. Plant collection
- 3.2.2. Extract preparation
- 3.2.3. Cell culture
- 3.2.4. HIV assay and cytotoxicity
- H-NMR analysis
- 3.2.6. Multivariate data analysis
- 3.3. Results and Discussion
- 3.4. Conclusion
- 3.5. References
Chapter NMR-based metabolomic guided fractionation and identification of anti-HIV active compounds
- 4.1. Introduction
- 4.2. Materials and Methods
- 4.2.1. Plant selection and collection
- 4.2.2. Extract preparation
- 4.2.3. Purification and Identification H-NMR analysis
- 4.2.5. Liquid chromatography – ion trap – time of flight mass spectrometry (LC-IT-TOF) characterisation
- 4.3. Results and Discussion
- 4.4. Conclusion
- 4.5. References
Chapter General Discussion
- 5.1 General Discussion
- 5.2 References
Chapter
- Acknowledgements
Chapter
- Appendix
- 7.1 NMR spectra of the water-methanol plant extracts
- 7. 1. 1. Helichrysum acutatum
- 7. 1. 2. Helichrysum allioides
- 7. 1. 3. Helichrysum anomalum
- 7. 1. 4. Helichrysum appendiculatum
- 7. 1. 5. Helichrysum aureonitens
- 7. 1. 6. Helichrysum cephaloideum
- 7. 1. 7. Helichrysum chionosphaerum
- 7. 1. 8. Helichrysum confertum
- 7. 1. 9. Helichrysum cymosum subsp. cymosum
- 7. 1. 10. Helichrysum cymosum subsp. clavum
- 7. 1. 11. Helichrysum difficile
- 7. 1. 12. Helichrysum drakensbergense
- 7. 1. 13. Helichrysum herbaceum
- 7. 1. 14. Helichrysum melanacme
- 7. 1. 15. Helichrysum miconiifolium
- 7. 1. 16. Helichrysum natalitium
- 7. 1. 17. Helichrysum nudifolium var. nudifolium (1)
- 7. 1. 18. Helichrysum odoratissimum
- 7. 1. 19. Helichrysum oreophilum
- 7. 1. 20. Helichrysum oxyphyllum
- 7. 1. 21. Helichrysum pallidum
- 7. 1. 22. Helichrysum panduratum
- 7. 1. 23. Helichrysum pannosum
- 7. 1. 24. Helichrysum pilosellum
- 7. 1. 25. Helichrysum pilosellum†
- 7. 1. 26. Helichrysum populifolium
- 7. 1. 27. Helichrysum rugulosum
- 7. 1. 28. Helichrysum splendidum (1)
- 7. 1. 29. Helichrysum subluteum
- 7. 1. 30. Helichrysum sutherlandii
- 7. 1. 31. Helichrysum umbraculigerum
- 7. 1. 32. Helichrysum vernum
- 7.2 NMR spectra of the dichloromethane (DCM) plant extract
- 7. 2. 1. Helichrysum acutatum
- 7. 2. 2. Helichrysum allioides
- 7. 2. 3. Helichrysum anomalum
- 7. 2. 4. Helichrysum appendiculatum
- 7. 2. 5. Helichrysum aureonitens
- 7. 2. 6. Helichrysum cephaloideum
- 7. 2. 7. Helichrysum chionosphaerum
- 7. 2. 8. Helichrysum confertum
- 7. 2. 9. Helichrysum cymosum subsp. cymosum
- 7. 2. 10. Helichrysum cymosum subsp. clavum
- 7. 2. 11. Helichrysum difficile
- 7. 2. 12. Helichrysum drakensbergense
- 7. 2. 13. Helichrysum herbaceum
- 7. 2. 14. Helichrysum melanacme
- 7. 2. 15. Helichrysum miconiifolium
- 7. 2. 16. Helichrysum natalitium
- 7. 2. 17. Helichrysum nudifolium var. nudifolium (1)
- 7. 2. 18. Helichrysum odoratissimum
- 7. 2. 19. Helichrysum oreophilum
- 7. 2. 20. Helichrysum oxyphyllum
- 7. 2. 21. Helichrysum pallidum
- 7. 2. 22. Helichrysum panduratum
- 7. 2. 23. Helichrysum pannosum
- 7. 2. 24. Helichrysum pilosellum
- 7. 2. 25. Helichrysum pilosellum†
- 7. 2. 26. Helichrysum populifolium
- 7. 2. 27. Helichrysum rugulosum
- 7. 2. 28. Helichrysum splendidum (1)
- 7. 2. 29. Helichrysum subluteum
- 7. 2. 30. Helichrysum sutherlandii
- 7. 2. 31. Helichrysum umbraculigerum
- 7. 2. 32. Helichrysum vernum
- 7.3 NMR spectra of the Sephadex fractions
- 7. 3. 1. Fraction
- 7. 3. 1. Fraction
- 7. 3. 1. Fraction
- 7. 3. 1. Fraction
- 7. 3. 1. Fraction
- 7. 3. 1. Fraction
- 7. 3. 1. Fraction