Communicable Diseases of the Developing World

258 Pages·2018·8.02 MB·English

by  Anil Kumar Saxena

Topics in Medicinal Chemistry 29
Anil Kumar Saxena Editor
Communicable
Diseases of the
Developing
World
29
Topics in Medicinal Chemistry
Editorial Board:
P.R. Bernstein, Philadelphia, USA
G.I. Georg, Minneapolis, USA
T. Keller, Singapore
T. Kobayashi, Tokyo, Japan
J.A. Lowe, Stonington, USA
N.A. Meanwell, Princeton, USA
A.K. Saxena, Lucknow, India
U. Stilz, Malov, Denmark
C.T. Supuran, Sesto Fiorentino, Italy
A. Zhang, Pudong, China
Aims and Scope
Drug research requires interdisciplinary team-work at the interface between
chemistry, biology and medicine. Therefore, the new topic-related series Topics in
Medicinal Chemistry will cover all relevant aspects of drug research, e.g.
pathobiochemistry of diseases, identification and validation of (emerging) drug
targets, structural biology, drugability of targets, drug design approaches,
chemogenomics,syntheticchemistryincludingcombinatorialmethods,bioorganic
chemistry,naturalcompounds,high-throughputscreening,pharmacologicalinvitro
and in vivo investigations, drug-receptor interactions at the molecular level,
structure-activityrelationships,drugabsorption,distribution,metabolism,elimina-
tion,toxicologyandpharmacogenomics.
Ingeneral,specialvolumesareeditedbywellknownguesteditors.
InreferencesTopicsinMedicinalChemistryisabbreviatedTopMedChemandis
citedasajournal.
More information about this series at http://www.springer.com/series/7355
Anil Kumar Saxena
Editor
Communicable Diseases
of the Developing World
With contributions by
(cid:1) (cid:1) (cid:1) (cid:1)
C.S. Azad S.S. Bhunia P. Eleftheriou M. Ferri
(cid:1) (cid:1) (cid:1)
A. Geronikaki R. Kalyanasundaram S. Pandey
(cid:1) (cid:1) (cid:1) (cid:1)
V. Poroikov A. Saxena A.K. Saxena P.K. Shukla
(cid:1)
P. Singh R.K. Yadav
Editor
AnilKumarSaxena
CentralDrugResearchInstitute
DivisionofMedicinal&ProcessChemistry
Lucknow,UttarPradesh
India
ISSN1862-2461 ISSN1862-247X (electronic)
TopicsinMedicinalChemistry
ISBN978-3-319-78252-2 ISBN978-3-319-78254-6 (eBook)
https://doi.org/10.1007/978-3-319-78254-6
LibraryofCongressControlNumber:2018937104
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Preface
Communicable diseases have always been a major concern to human health,
particularly in the developing world where millions of people die every year.
This scenario is changing with increased human mobilization and immigration
coupled with trading of foodstuffs and biological products and so communicable
diseases are no more localized but may affect population worldwide. Furthermore
therapidadaptationbymicroorganismsisleadingtotheresurgenceofcommunicable
diseases of the past, drug resistance to the existing diseases, and the emergence
of new ones. Most of the communicable diseases have not been paid adequate
attention by the developed world. These diseases include malaria, tuberculosis,
leishmaniasis,filariasis,dengue,HIV/AIDS,diarrhea,cholera,leprosy,buruliulcer,
trachoma, and schistosomiasis. In view of this, a book volume covering tuberculo-
sis,malaria,kinetoplastids, denguefever,and diarrheawas publishedinthe Topics
in Medicinal Chemistry series by Prof. Richard L. Elliott. Following this previous
publication and considering the recent outbreak of Ebola virus disease, the present
volumeentitledCommunicableDiseasesoftheDevelopingWorldwasenvisagedto
cover leftover diseases including a chapter on Ebola. So the important diseases
suchasHIV/AIDS,filariasis,fungalinfections,andneglectedvirusdisease,bacterial
diseasesincludingEbolavirusdiseasehavebeendescribedinthefivechaptersofthis
volume.ThefirstchapteronEbolavirusdiseasedealswithitsclinicalmanagement
and the control measures to be followedalong with the current status ofdrugs and
vaccinedevelopmentforthepreventionandcureofthisdisease.Inthesecondchapter
the current state ofHIV therapeutics aswell asthe status ofcandidate drugs under
development along with the future prospects of HIV treatment has been dealt. The
third chapter is on the important neglected parasitic disease known as lymphatic
filariasis where the targets and strategies for intervention and elimination of this
diseasealongwiththeexistingchemotherapyandnewerdevelopmentsforlymphatic
filariasisaredescribed.Thefourthchapterisontheantifungalagents,whichprovides
anoverviewofthepast,present,andfutureprospectsofdrugs,cationicpeptides,and
monoclonal antibodies as antifungal agents. The fifth chapter covers neglected
v
vi Preface
tropical bacterial diseases like leprosy, buruli ulcer, and trachoma along with the
chemotherapeuticapproachestotheirtreatment.
It has been an immense pleasure to be the editor of this volume. I gratefully
acknowledgealltheauthorsfortheircontributionsandthankthemfortakingtime
and care in composing the chapters. I wish that this volume will be useful for
researchers working on these diseases and will inspire many more to develop
strategiesforthediscoveryanddevelopmentofnewtherapiesforthesediseases.
Lucknow,India AnilKumarSaxena
Contents
ClinicalManagementofEbolaVirusDisease:CurrentandFuture
Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
AaruniSaxenaandMauricioFerri
Anti-HIVAgents:CurrentStatusandRecentTrends. . . . . . . . . . . . . 37
AthinaGeronikaki,PhaedraEleftheriou,andVladimirPoroikov
LymphaticFilariasis:CurrentStatusofEliminationUsing
ChemotherapyandtheNeedforaVaccine. . . . . . . . . . . . . . . . . . . . . 97
RamaswamyKalyanasundaram
Past,Present,andFutureofAntifungalDrugDevelopment. . . . . . . . 125
P.K.Shukla,PratikshaSingh,RavindraKumarYadav,SmritiPandey,
andShomeS.Bhunia
NeglectedTropicalBacterialDiseases. . . . . . . . . . . . . . . . . . . . . . . . . 169
AnilKumarSaxenaandChandraSourabhAzad
Erratumto:Anti-HIVAgents:CurrentStatusandRecentTrends. . . 245
AthinaGeronikaki,PhaedraEleftheriou,andVladimirPoroikov
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
vii
TopMedChem(2018)29:1–36
DOI:10.1007/7355_2015_5003
©SpringerInternationalPublishingSwitzerland2015
Publishedonline:12August2016
Clinical Management of Ebola Virus
Disease: Current and Future Approaches
AaruniSaxenaandMauricioFerri
Abstract Ebola virus disease (EVD) is a notoriously dreadful disease. The acute
viral syndrome, which has an incubation period ranging from 2 to 21 days, is
characterizedbyfeveranddiarrhea,alongwithbleedingdiathesis.Mortalityrates
are high. The natural reservoir is thought to be the fruit bat of the Pteropodidae
family. Nonhuman primates, including monkeys, chimpanzees, and gorillas, are
primaryhoststothevirus.Transmissionoccursthroughdirectcontactwithbodily
fluids containing the virus. Currently available laboratory tests include the rapid
diagnostic tests ELISA and PCR. A patient’s chance of survival depends on
multiplefactors,suchastheinitialviralloadatthetimeofexposure,theirimmune
response to the virus, and access to proper care. Currently, there is no specific
treatment or cure; however, clinical management mainly consists of supportive
measures.Noveldrugsandvaccinesareundergoingclinicaltrialstodeterminetheir
safetyandefficacyforuseinhumans.
Keywords Drugs,Ebolavirusdisease,Epidemic,Protection,Treatment,Vaccines
Contents
1 Introduction.................................................................................... 2
2 Epidemiology.................................................................................. 3
2.1 GeographicSpreadofEbolaoverTime................................................ 3
2.2 Transmission............................................................................. 3
2.3 Surveillance.............................................................................. 4
2.4 CaseInvestigation....................................................................... 4
Theonlineversionofthischapterhasbeenrevised.
A.Saxena
ClinicalPraxis,Schulstrasse36,Hilden40721,Germany
M.Ferri(*)
HealthServiceResearch,RedeMetropolitanadeSau´de,Sarand´ı,Brazil
e-mail:[email protected]
2 A.SaxenaandM.Ferri
2.5 ContactTracing......................................................................... 6
2.6 ControlMeasures....................................................................... 6
3 Pathology..................................................................................... 7
4 ClinicalPresentationandLaboratoryDiagnosis............................................ 11
4.1 ClinicalPresentation................................................................... 12
4.2 LaboratoryFindings.................................................................... 13
5 ClinicalManagement:CurrentandFutureApproaches..................................... 15
5.1 SupportiveCare........................................................................ 15
5.2 Vaccines................................................................................ 16
5.3 NovelCompoundsandDrugs.......................................................... 19
6 Conclusion.................................................................................... 29
References........................................................................................ 29
1 Introduction
Ebolavirusdisease(EVD)firstappearedin1976,simultaneouslyintheDemocratic
RepublicofCongo(DRC)andSudan[1].Ebolavirus(EBOV)belongstothevirus
family Filoviridae [2]. Apart from the Ebola virus, the other main member of the
familyistheMarburgvirus.ItwasdiscoveredearlierthantheEbolavirus,in1967.
ThediscoverytookplaceafterseveralcommerciallaboratoryworkersinGermany
were admitted to hospital with an unusual illness. The clinicians observed a
different pattern of clinical symptoms in each patient but a similar course of
disease.Furtherinvestigationrevealedthesourceofinfectiontobeavirusisolated
fromgreenmonkeysimportedfromAfricaforresearchpurposes.Quarantinepro-
ceduresweresubsequentlyimplementedtohaltfurthertransmission,andcountries
advisedtoexercisecautionwhenimportingmonkeys[3].
Ebola is the second known Filovirus and can be more lethal than the Marburg
virus. It was often reported in cynomolgus monkeys (Macaca fascicularis) in the
earlyandlate1990s[4,5].Ebolainhumanswasseenagainfrom1994to1996.This
time the infection included the subtype Zaire ebolavirus (EBOV-Z) and a new
subtype known as Coˆte d’Ivoire ebolavirus (EBOV-CI) or Ta¨ı Forest ebolavirus
[6]. At the time, little was known about the occurrence and transmission of the
Ebola virus. Later, three more species were discovered and added to the genus
Ebolavirus: Bundibugyo, Reston, and Sudan. The Bundibugyo, Zaire, and Sudan
viruseshavebeenresponsibleforoutbreaksinAfrica;theRestonvirusispredom-
inantly found in animals [7, 8]. After long-running discussion, the scientific com-
munity concluded that fruit bats of the Pteropodidae family may likely be the
natural hosts of the Ebola virus. The fruit bat species includes Hypsignathus
monstrosus, Epomops franqueti, and Myonycteris torquata [9, 10]. All other ani-
mals infected by Ebola, especially monkeys, gorillas, and chimpanzees, are acci-
dentalhosts[11,12],althoughthereremainsthepossibilityofothernaturalhosts.
Researcheffortshavebeencomplicatedbythelethalnatureofthevirus.