(cid:19)(cid:19)(cid:19)(cid:19)(cid:19)(cid:20)
`
`Petition for Inter Partes Review
`Of U.S. Patent 8,278,351
`Exhibit
`ENZYMOTEC - 1018
`
`

`

`
`
`WHO News and activities
`
`—— clarification of the significance of the reduction
`in muscarinic receptor density caused by DDT.
`
`Control of epidemic meningococcal
`disease
`
`Meningococcal disease occurs in two clinical forms:
`meningococcal meningitis and meningococcal septi-
`caemia. Of these,
`the former
`is commoner, but
`responds well to treatment. In contrast, meningococ-
`cal septicaemia, although less common, is fatal, even
`when actively treated. Meningococcal meningitis is
`the only form that causes epidemics. These can occur
`anywhere in the world; however, the largest occur
`mainly in the semi-arid areas of sub-Saharan Africa
`(African meningitis belt) Apart
`from epidemics,
`mAllvlnllnev
`”unnubu
`vvvulu
`unflvluulvul
`pninnncnccal
`mpnInaihS
`nr‘t‘nrc
`sunrnl‘hl‘uily
`throughout the world, with seasonal variations, and
`accounts for a variable proportion of endemic bac-
`terial meningitis
`A 71--page booklet containing practical guide—
`lines on the control of meningococcal disease for
`health personnel and 118211111 3111110111183, at any level,
`has recently been prepared by a WHO Working
`Group.“ The five chapters cover a range of topics,
`the most important of which are outlined below.
`
`o The magnitude of the problem: review of epidem-
`ics of meningococcal disease since 1970 (periodicity
`and seasonality of the epidemics, epidemic patterns);
`conditions
`favouring epidemics
`(serogroups
`and
`sergtypgg immunity and damngmnhic
`factors);
`and meningococcal meningitis as part ‘of bacterial
`meningitis (endemic meningococcal disease, other
`causes U1 1136161141 Illellillgllis).
`
`o The disease. how to recognize and confirm
`meningococcal disease (signs and symptoms, physi—
`cal examination, lumbar puncture and cerebrospinal
`fluid (CSF) examination, differential diagnosis); how
`to manage patients with meningococcal disease (anti-
`microbial
`therapy,
`supportive therapy,
`simplified
`management under difficult conditions); how to pre—
`.................................
`vent memnonr‘nr‘r‘al disease (vaccinatinn
`chemn—
`
`o How to plan for and respond to an epidemic:
`national/provincial crisis committee;
`informing the
`public; planning an appropriate emergency response
`(vaccination, chemoprophylaxis, general measures);
`Ann“: nn- anr111 rln
`”In mrln
`sustaining the control programme and ensuring
`Auuuw- uy, auu uUCulllelllillg cue Cpiupuuc.
`
`o Interepidemic prophylaxis. containment around a
`patient with meningococcal disease in non-epidemic
`conditions; routine vaccination; and regulations for
`travellers.
`
`together with 10 annexes that prov1de
`included,
`information on the following:
`
`- Gram and methylene blue staining;
`
`—— latex agglutination tests;
`
`—— injecting oily chloramphenicol;
`— vaccines;
`_ mrhlir‘
`dnmain
`
`e0 tw re
`
`investigations;
`— materials for field investigations;
`— materials for diagnosing Neisseria meningitidis;
`
`— preparing trans-isolate medium;
`— sources of kits for mass vaccination campaigns;
`and
`
`— organizing a vaccination campaign.
`
`Single copies of this booklet can be obtained
`from the Programme on Bacterial, Viral Diseases
`and Immunology, Division of Communicable Dis-
`eases, World Health Organization, 1211 Geneva 27,
`Switzerland.
`
`Yellow fever in 1992 and 1993’
`
`prophylaxis).
`
`The total numbers of cases of yellow fever in 1992
`and 1993 were relatively low, but noteworthy in that
`1116 11151 UulUleak leCUlueU 111 KEuya $11166 1943 was
`documented. A total of 295 cases were reported to
`WHO for 1992, with 102 deaths (case—fatality rate
`(CFR), 35%). These included 176 cases and 21 deaths
`(CFR, 12%) from Africa, and 119 cases and 81
`o How to detect and confirm an outbreak or epi-
`[Ha
`Andllfimdn "Ann-n
`deaths (CFR, 68%) from South America. In 1993, a
`elJlUCllllU VUIDUD
`“C"llb (If llltlll’LSULULLul ulSé/‘uSé’C
`total of 218 cases and 38 deaths (CFR, 17%) were
`endemic disease; planning and implementing an
`reported from Africa, and 175 cases with 79 deaths
`early warning system (collecting and reporting infor-
`(CFR, 45%) were documented from South America,
`mation, regular data review, deciding when an epi—
`for a grand total of 393 cases and 117 deaths (CFR,
`demic is occurring); rapid assessment of a suspected
`30%). A summary of the number of yellow fever
`epidemic of meningococcal disease (investigation of
`cases and deaths reported to WHO by Member States
`suspected cases).
`for the period 1989-931s shownin Table 1.
`
`
`" Control of epidemic meningococcal disease: WHO practical
`guidelines. Lyon. Edition Foundation Marcel Mérieux, 1995.
`
`’ Based on: Yellow fever in 1992 and 1993. Weekly epidemio-
`logical record, 1995, 70(10): 65—70.
`
`548
`
`WHO Bulletin OMS. Vol 73 1995
`
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`000002
`
`AKER877ITCOO739748
`
`

`

`
`Tabie 1
`‘I'Eiié‘v'v 1‘ver numher ‘1 cases and deaths (ease-f t‘iity r‘t‘) notified to WHG, 193” 93
`1989
`1990
`1991
`1992
`1993
`
`WHO News and activities
`
`
`Country/area
`Cases
`Deaths
`Cases
`Deaths
`Cases
`Deaths
`Cases Deaths
`Cases Deaths
`Africa
`Cameroon
`Ghana
`
`——
`—
`
`—
`—
`
`173
`—
`
`1 1 8
`—
`
`——
`—
`
`—-
`—
`
`—
`—
`
`—
`—
`
`39
`
`15
`
`Kenya
`-—
`——
`—
`—
`—
`—
`27
`
`Nigeria
`3 270
`618
`4 075
`223
`2 561
`661
`149
`
`Total
`3 270
`618 (19)"1
`4 248
`341 (8)
`2 561
`661 (26)
`176
`South America”
`14
`18
`18
`22
`54
`91
`38
`so
`87
`107
`Bolivia
`17
`66
`8
`12
`8
`15
`1
`2
`3
`9
`Brazil
`1
`1
`2
`2
`4
`4
`7
`7
`1
`1
`Colombia
`Ecuador
`—
`——
`12
`6
`14
`9
`1 6
`13
`1
`-—
`Peru
`120
`100
`17
`17
`27
`15
`67
`40
`89
`47
`
`
`27
`152
`218
`
`15
`8
`38 (17)
`
`13
`8
`21 (12)
`
`Total
`
`Grand total
`
`237
`
`3 507
`
`191 (81)
`
`809 (23)
`
`88
`
`69 (78)
`
`151
`
`90 (60)
`
`4 336
`
`410 (9)
`
`2 712
`
`751 (28)
`
`119
`
`295
`
`81 (68)
`
`102 (35)
`
`175
`
`398
`
`79 (45)
`
`117 (30)
`
`3 Figures in parentheses are percentages.
`b The case pretlinnslu repnn‘ed in French Guiana in 1990 h
`
`as been eieted.
`
`nu .vu
`A rut-2
`
`In a dramatic decrease in the number of cases repor-
`ted compared with previous years, only Kenya and
`Nigeria reported yellow fever in 1992, while Ghana
`experienced a limited outbreak in 1993 that con-
`tinued into 1994.
`
`In 1993, an outbreak of yellow fever
`Ghana.
`occurred in the Upper West Region, with 39 cases
`and 15 deaths (CFR, 38%)!" The outbreak began in
`October 1993 and cases were still being reported in
`December Transmission anneared tn he limited in
`the Jiripa District Yellow fever was confirmed sero-
`logically. Of 37 cases where age and sex were
`reported, 15 (40%) were under 15 years of age, and 9
`(24%) were females. An immunization campaign
`100A unann—n on Inn
`”Ankh11AA ”In
`Lei-An],
`was begun in December 1993 and continued into
`177*; ll OPPCCUB lU llaVe VUIltlUlleU llle UULUICM.
`
`Va
`1011’! I.nnnnnn on ("M“L 100’) nnAn
`Kenya. The first yellow fever outbreak reported from
`1\cuya SiuC€
`171'.) wsau Au uepLDHIWl 1771. allu Cun-
`tinued through March 1993. The outbreak was limit-
`ed to the Baringo and Elgeyo Marakwet Districts in
`the Kerio Valley, north-west of Nairobi. A total of
`54 cases and 28 deaths (CFR, 52%) were recorded.
`Eighteen of the cases (33%) were among people
`aged 519 years and 19 cases (35%) were femaies.
`Epidemiological
`investigations
`indicated that
`the
`outbreak was consistent with jungle yellow fever.
`The virus was isolated from clinical specimens of ill
`
`m Yellow fever, Ghana. Weekly epidemiological rr-zieord= 1994,
`69(6): 44; and 1994, 69(10): 76.
`
`w.“ “at“.
`and fatal
`
`(‘QQPC
`vuuvu,
`
`u-vu‘lunuvu-
`caprnrsd mncnlnfnc
`Molecular characterization of the isolated viruses
`
`Al vu-
`
`indicated that they were similar in genetic composi—
`tion to those previously isoiated from humans and
`mosquitos during past outbreaks of yellow fever in
`East Africa, and genetically distinct from isolates
`from specimens collected in West Africa or South
`America. The outbreak was halted following a mass
`immunization campaign, during which nearly 1 mil-
`lion doses of yellow fever vaccine were administered
`to residents of the areas at risk.
`
`Nigeria. Only 149 cases and 8 deaths (CFR, 5%)
`were reported from Nigeria in 1992, unlike the situa-
`tion in recent years when several
`thousand cases
`were documented. In 1993, 152 cases were reported,
`with eight deaths (CFR, 5%). No information was
`provided on the specific dates of onset,
`locations,
`age or sex of the reported cases for either year.
`
`EPi: yéiiéw fever Vaccine in Africa. Since 1989,
`WHO/EPI has recommended that yellow fever vac-
`cine be included in the childhood immunization pro-
`glalllllles U1 [He 33 UUullllleS ill Afllca al. 118k fUI llle
`disease. Today, 17 of the 33 countries have a nation-
`al policy to this effect. Up to August 1994, yellow
`fever immunization coverage data had been reported
`to WHO by 15 of the 17 countries. Burkina Faso, the
`Gambia, and Mauritania have achieved coverage
`above 50% for children by their first birthday. How-
`ever, for all 33 African countries at risk for yellow
`fever, vaccine coverage levels only reached 7% in
`1993, compared with 11% in 1992.
`
`WHO Bulletin OMS. Vol 73 1995
`
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`

`

`WHO News and actlvltles
`
`The African countries at risk are among the
`most impoverished countries in the world. Although
`yellow fever vaccine is available to developing coun-
`tries at less than US$ 0.25 per dose, this price is still
`a barrier to many countries at
`risk. Donors are
`encouraged to provide assistance to help the African
`countries at risk prevent the deadly disease through
`routine immunization.
`
`South America
`
`In 1992, a total of 119 cases and 81 deaths (CFR,
`63%) were officially reported from South America:
`22 cases and 18 deaths (CFR, 82%) were reported
`from Bolivia; 12 cases and 8 deaths (CFR, 67%) from
`Brazil; 2 cases and 2 deaths (CFR, 100%) from
`Colombia; 16 cases and 13 deaths (CFR, 81%) from
`Ecuador and 67 cases and 40 deaths (CFR, 60%)
`from Peru.
`
`In 1993, 18 cases and 14 deaths (CFR, 78%) were
`reported from Bolivia, 66 cases and 17 deaths (CFR,
`26%) from Brazil; one fatal case from Colombia; one
`non-fatal case from Ecuador; and 89 cases with 47
`deaths (CFR, 53%) from Peru. Thus, a total of 175
`cases were reported, with 79 deaths (CFR, 45%).
`
`Boliyln All 2.2. cases that occurred dunr1ng 1992 were
`among adult males aged 16—70 years. A total of 16
`cases were reported from La Paz Department, 1 case
`from Cochabamba, and 5 cases from Santa Cruz.
`Eighteen of the 22 cases were fatal,
`including all
`A! Ln nnnnn
`Ga ”1» I‘m
`f‘n
`all 0km nln
`those from La Paz, the case in Cochabamba, and one
`U1 ulc baoco 1P1 aat'ha L1uZ. bases uCCLuICu uuu'usu-
`out the year. Of the 18 cases reported in 1993,14
`were from La Paz and 4 from Santa Cruz: 13 of the
`
`14 patients from La Paz and 1 of the cases from
`Santa Cruz died. Three cases involved females aged
`6 months, 30 years, and 70 years. The youngest and
`the oldest were among the fatai cases. The ‘15 maie
`cases were aged 7—57 years; 12 died.
`
`Brazii. Of 12 cases reported in 1992, all were among
`young adult males except one, a 21—year-old woman
`who died on 1 January 1992 in Sidrolandia, Mato
`Grosso do Sul State. The male cases were aged
`18—39 years (1 was aged <20 years; 4 were aged
`20—29 years; 6 were aged 30—39 years). A total of
`eight cases were reported from Mato Grosso do Sul
`State, two from Mato Grosso, and one each from
`Amazonas and Roraima. Six cases occurred in Janu-
`ary, one in February,
`three in March and two in
`November.
`vv-tv- -N- v. J vA-v
`I11 1993 m1 nuthrenlr nf vellnw fgver 001311qu
`between March and May around the Municipality of
`Mirador in the State of Maranhao. Of the 66 cases
`
`reported. 44 were from this location, and an addi-
`tional 11 were from Barra do Corda in the same
`
`550
`
`state. A total of 17 deaths were reported (CFR,
`26%), but only three were from Mirador and four
`from Barra do Corda.
`
`Colombia. In 1992, two fatal cases of yellow fever
`involving young men were reported in Florencia,
`Caqueta Province, and Puerto Asis, Putumayo Prov-
`ince. No additional epidemiological information was
`reported for these cases. In 1993 one fatal case was
`reported in Zaragoza, Antioquia Province.
`
`Ecuador. Epidemiological information was available
`for 11 of the 16 cases reported in 1992. All were
`among young men, with seven aged less than 20
`years, two aged 20—29 years, and two aged 40—49
`years. The dates of onset were May (3 cases) and
`June (8 cases), and the localities affected were Pasta-
`1 Havuuv
`vuuw, ,MF \
`H...
`Z3. Drnvinnn (4 racpc\ Nnnn ('2 cases) and Sncnmbr-
`0s (3 cases); no information was provided for one
`case. In 1993 one case was reported but no epidemi-
`ological information was given.
`
`Peru. Peru accounted for the largest number of cases
`nnt1fied 111 the. American Region in 1992. and 1993.
`In 1992,67 cases were reported, of which 40 were
`fatal (CFR, 60%) and in 1993, 89 cases and 47
`"T'L--....LA..‘
`inno ,r-
`ans—1 Al!
`1111uuguuu1 1774, a lUldl U1
`deaths (CFR, 53%).
`l— 12 cases were notified monthly. A total of 35
`cases were from seven provinces in the Department
`A? Sun ”Innu’n 'T'kn
`('1’, nocon “row: rannrfn
`UL uau 1v1cuuu.1.uv Lelualuulg J1. vaava Wv1v 1vyv11vu
`in 13 provinces in seven departments. A total of 56
`of the 67 cases were in patients over 15 years of age,
`and 43 were aged 20—40 years.
`Of the 89 cases notified in Peru in 1993, a total
`of 80 were from the Departments of San Martin (32),
`Junin (28) and Ayacucho (20). The highest number
`of cases in San Martin Department were reported
`from Huallaga Province (17 cases), in Junin Depart-
`ment from Chanchamayo Province (21 cases), and in
`Ayacucho Department from Lucanas Province (12
`cases). Six other provinces in San Martin,
`two in
`Junin and 12 in Ayacucho reported cases, and the
`"F“ m (In
`ntc Qn‘ranlnnn n? ”In 90 nacnc
`remaining nine cases were scattered over six prov-
`111Ces 111 lev uvpasuueula. uwvuulvvu v1. Luv u/ vuovo
`were in females, 15 cases were 15 years of age, and
`three were >60 years of age.
`
`Conclusion
`
`The risk of yellow fever in many tropical and sub-
`tropical areas of Africa and South America continues
`to be significant. The disease remains enzootic in
`these areas in a jungle cycle, with.
`transmission
`occurring primarily among non—human primates,
`with forest-dwelling mosquitos serving as vectors.
`Humans are infected when they enter into areas of
`active transmission and are fed upon by infectious
`
`WHO Bulletin OMS. Vol 73 1995
`
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`
`

`

`
`
`mosquitos. A greater risk f‘r human epidemic trans-
`mission occurs when viraemic persons enter urban
`centres where they may be fed upon by competent
`domestic mosquito vectors, especially Aedes aegypti.
`The re-infestation of many tropical and subtropical
`cities by this mosquito species is of grave concern in
`the light of historical urban yellow fever outbreaks,
`and the realization that both human and vector mos-
`
`quito population densities are now much greater than
`when urban yellow fever was last commonplace.
`
`Nutritional value of Antarctic krill"
`
`A healthy diet requires a proper balance of carbohy-
`drates, proteins, fats (and oils), fibre and minerals, as
`well as other nutrients. Nutritionally, Antarctic krill
`(Euphausia superba) appears to be a food appropria«
`te for inclusion in a healthy diet;
`it contains equal
`proportions of polyunsaturated, monounsaturated,
`and saturated fatty acids, with the last-mentioned
`accounting for less than 6% of the total energy
`content; and it has a high protein content (63.7% of
`dry weight of the meat).
`Of the more than 70 species of euphausiid crus-
`ova “vacant
`"1 (11¢ Annntrnl‘nm n0 fkn
`tannunc that
`luvvuuo uuu
`WU PIVDVIII
`lll Lllv UUUDJDLUILI UL Lily
`
`south~westem Atlantic Ocean, the largest is Antarc-
`tic krill, which can reach up 5—6 cm in length. Ant-
`arctic krill occurs throughout the circumpolar zone,
`but is especially abundant in the waters surrounding
`the South Shetland Isles. The total estimated reserves
`of the crustacean are enormous (500-2500 million
`tonnes) and an annual catch of only 10% of this bio-
`mass would be equivalent to the world’s total yearly
`fish catch. Work on its use as a foodstuff for human
`
`consumption has been carried out in several coun—
`
`
`
`" Summary of an article submitted by B.A. Grillo, W. Alallon,
`and P. Louisot. Copies of the full article can be obtained upon
`request
`from Dr Grillo, Bvar. Espana 2575/402, Montevideo
`11300, Uruguay.
`
`WHO News and activities
`
`rv,
`tries, e.g., Russian rederation, Poland, Japan, Chile,
`and Uruguay.
`is low
`level of Antarctic krill
`The cholesterol
`(ca. 30 mg per 100 g), while the level of polyunsatu-
`rated fatty acids of the n—3 series (principally octa-
`decatetraeonic
`acid,
`eicosapentaenoic
`acid,
`and
`docosahexaenoic acid) is high (1.47 g per 100 g). The
`total level of polyunsaturated fatty acids is similar to
`that of tuna, salmon, anchovy, and herring.
`Noteworthy is the high selenium content of Ant—
`arctic krill (3.41 pg/g), a trace element that is a co—
`factor for glutathione peroxidase. Other trace ele-
`ments present include zinc (43.7 ug/g) and copper
`(4.77 pg/g), both of which play a role in the action of
`superoxide dismutase.
`Studies on rabbits indicated that replacement of
`10% of their basal diet with krill produced a reduc-
`tion (P<0.05) in formation of atherornatous plaque;
`also,
`the levels of aortic and pulmonary plaque
`caused by a hypercholesterolaemic diet were reduced
`in roklniro fknt “mm For} brill
`u: AuuunLo um; wvlv Avu mun.
`
`Controlled studies on humans suggest that con-
`sumption of 25 g per day of Antarctic krill meat for
`7 days could significantly reduce platelet aggregation
`and increase plasma levels of eicosapentaenoic acid
`and docosahexaenoic acid. Furthermore, a krill diet
`may have a pronounced anti‘atherogenic effect, as
`indicated by the marked reduction or elimination of
`the atherogenic potential
`it produces on the blood
`plasma of patients with cardiac insufficiency,
`in-
`ducing an in-vitro reduction in the incorporation of
`cholesterol into the subendothelial cells of the aorta.
`
`The organoleptic properties appear to be retained
`in krill meal stored for up to 6 months at tempera-
`tures below 20 °C and for over 8 months at tempera=
`tures of 4—8 °C. The authors report that Antarctic
`krill meat has no hepatotoxic effects and that it may
`have beneficial effects on chronic diseases such as
`
`atherosclerosis. Other products that can be derived
`from Antarctic krill, e.g., chitosans from the shell,
`astaxanthins, proteolytic
`and lipolytic
`enzymes,
`together with exploitation of its high fluorine con-
`tent, represent novel areas for research.
`
`WHO Bulletin OMS. Vol 73 1995
`
`551
`
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`000005
`
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`
`

`

`Notes et activités OMS
`
`Utilisation du DDT dans la lutte
`
`antivectoriellea
`
`De nombreux pays utilisent 1e DDT dans la lutte
`contre le paludisme et contre la leishmaniose viscé-
`rale. Toutefois, 1’hypothése d‘une association entre
`l’utilisation du DDT et la survenue de cancers chez
`
`l’homme a été récemment avancée;"-c un rapport sur
`la presence de DDT dans le lait matemel a été
`publié,d et deux mises au point générales sur l’utili-
`sation du DDT dans la lutte antivectorielle ont été
`réalisées.e Le Groupe d’étude dc l’OMS sur le palu-
`disme et les autres maladies transmises par les mous-
`tiques,
`1.1111
`s ’est
`réuni a Geneva du 16 au 24
`novembre 1993, était charge, entre autres questions,
`d’examiner la situation actuelle a la lumiere des pro-
`..-kn -Knnacn ,AnlinAn Anna nix Anmn:mn hnnu (“um-“um
`5163 leClllb lCallBCD uaua \wC UUHIGIIIC. UCUA CAPE/Ila
`
`toxicologues ont été, a cette fin, invites a participer
`ma
`aux travaux du Groupe. ’ Les conclusions du Groupe
`yquu vuuyqumu I quIauqu
`VI uullo I“
`d’ArnAa nnnnn
`fl’nhlioohnn d" DDT Home 10 lull-e
`antivectorielle, resultant des discussions entre l’en-
`semble des participants, sont résumées ci-dessous.
`
`o L’information présentée n’offre pas de preuves
`suffisantes ni convaincantes des effets indésirables
`
`dc l’exposition au DDT resultant des pulvérisations a
`effet rémanent a l’intérieur des habitations telles
`
`qu’elles sont pratiquées dans 1e cadre de la lutte anti-
`paludique.
`o Dans 1’e’tat actuel des connaissances, rien ne justi—
`fie,
`tant sur le plan toxicologique qu’épidémiolo-
`
`
`‘4 D’apres: Vector control for malaria and other mosquito-borne
`ui‘seases (Annexe 1). Geneva, Organisation mondiale de la
`Santé (OMS, Série de Rapports techniques), sous presse (ver-
`sion frangaise en préparation).
`b Garabrant DH et at. DDT and related compounds and risk of
`pancreatic cancer. Journal of the National Cancer Institute,
`1992, 84: 764—771.
`C Wolff M5 at al. Blood levels of organochlorine residues and
`risk oi breast cancer. Journal of the National Cancer institute.
`1993. 85: 648—652.
`4 Bouwman H et al. Levels of DDT and metabolites in breast
`miik from Kwa-Zuiu mothers after DDT appiicaiion for maiaria
`control. Bulletin de I’Organisation mondiale de la Santé, 1990,
`68: 761—768.
`9 Par: Dr C.F. Curtis, Department oi Medical Parasitology, Lon-
`don School 01 Hygiene and Tropical Medicine, Londres, Angle-
`terre, et Protesseur J. Mouchet,
`lnstitut trancais de Recherche
`Scientifique pour le Développement en Cooperation (ORSTOM),
`Paris, France.
`' Dr W.N. Aldridge, The Roben's institute, Kings Worthy, Hants,
`Angleterre, et Protesseur M. Lotti, Institut de Médecine du Trav
`vuu, vulvoiauc no 1
`uvuvi
`I
`v, uuuv.
`unil
`llniunrcilé dc Dad""° Dad""e Italic
`5' Place du DDT dans les operations contre la paludisme et
`autres maladies transmises par des vecteurs. In: Conseil execu-
`tif, Ouarante-septieme session, Geneve, 19—29 janvier 1971,
`
`Tiré a part N” 5633
`
`
`
`gique, de modifier 1a politique en vigueur en matiére
`dc pulvérisations de DDT a l’intérieur des habita—
`tinns dams 1e satire. de la lutte cnntre, les maladies
`
`transmiseslpar des vecteurs.9
`0 Le DD peut donc étre utilisé dans la lutte anti-
`vegtn1-1gllg it cnqd1t1nn nnP tmltec 19c cnnditinne eni—
`vantes s01ent remphes.
`
`—— il ne doit étre utilisé que pour les pulvérisations a
`l’intérieur dcs habitations;
`
`— il doit étre efficace;
`
`_ Ie prndn1t dn1f étre fabnnl"3’ onnfnrmfimpnt any
`normes publie’es par l’OMS;”
`— les mesures de sécurité nécessaires doivent étre
`
`prises lors de son utilisation ct dc son elimina-
`tion.
`All
`3W
`.
`vernements devraicnt temr compte des facteursssup-
`plémentaires suivants:
`
`140
`nn'l‘uu
`I , Iva
`
`— cofit de l’emploi d’insecticides (DDT ou insecti-
`cides de remplacement);
`— ré‘ie des insecticides dans la lutte antivectorielie
`
`ciblée ou selective, comme il est spécifié [dans la
`Strategic mondiale de lutte antipaludiqueflrl
`— existence d’autres méthodes de lutte antivecto-
`
`rielle, y compris avec des insecticides de templa—
`cement (étant donné l’existence d’autres insecti—
`cides utilisablcs pour les pulvérisations a effet
`rémanent a 1’ inte’rieur des habitations, dont cer-
`l-n
`nnnuant nnnnIII-rnnnar In “111" (war '3 "Inn [in
`talus Punt/Ian vuuvunlpuvvl Iv uul aul II, yqu u\,
`1’ impact épidémiologique, de 1’ acceptabilité par
`le public, de 1’intérét logistique et de la confor—
`mité aux normes pubiiées par POMS, 1e DDT ne
`mérite plus d’étrc considéré comme l’insecticide
`de choix);
`
`—— consequences sur le plan de la resistance aux
`insecticides, y compris une éventuelle resistance
`croise’e avec certains insecticides de remplace-
`ment;
`
`
`
`Partie ll. Rapport sur le projet de programme at de budget pour
`1972. Geneve, Organisation mondiale de la Santé, 1971 (Actes
`officials de l'Organisation mondiale de la Santé, N"
`1.90):
`176—182.
`
`” Specifications for pesticides used in public health — insecti-
`cides: DDT. Document non publié WHO/CTD/WHOPES/QS,
`1993. Normes WHO/SIT/1.Fl7 et WHO/SlF/1.R7.
`" Stratégie mondiale de lutte antipa/udique. Geneve, Organisa-
`tion mondiale de la Santé, 1994.
`i Mise en oeuvre de la stratégie mondiale de lutte antipaludique.
`Rapport d’un groupe d’étude de l’OMS sur la mise en aeuvre du
`plan mondial d'action pour
`la
`lutte contre la paludisme
`1993_gnnn_ Genéun Organisafinn mondia1e de 13 331111; 1993
`(OMS, Série de Rappons techniques, N° 839)
`
`Bulletin de [Organisation mondiale do la Santa, 1995, 73 (4): 553-558
`
`© Organisation mondiale de la Santé 1995
`
`553
`
`(cid:19)(cid:19)(cid:19)(cid:19)(cid:19)(cid:25)
`000006
`
`AKER877ITCOO739752
`
`

`

`
`
`Notes et actlvités OMS
`
`—- évolution de l’attitude du public vis—A—vis de
`l’utilisation des pesticides, y compris dans le
`domaine de la santé publique.
`
`o Etant donné la minceur des données évoquant un
`éventuel effet indésirable des pulvérisations a effet
`rémanent a i’in‘térieur des habitations,
`ii convient
`d’encourager de nouvelles recherches epidemiolo-
`giques
`reposant
`sur des protocoles
`scientifiques
`rigoureux.
`0 De nouvelles études devraient également étre réa-
`lisées dans les domaines suivants:
`
`—— examen des effets du DDT présent dans le lait
`maternal sur la santé des nourrissons allaités au
`
`sein, y compris d’éventuels effets comportemen—
`taux;
`
`— etude approfondie de toute association évenruelle
`entre l’utilisation du DDT dans les activités cou-
`
`rantes de lutte antipaludique et une incidence
`accrue des cancers;
`
`— elucidation de la signification de la reduction de
`la densité des récepteurs aux muscariniques due
`au DDT.
`
`trite contre les édpié.11363 66
`méningite a méningocoque
`u... “IVIu-Iev
`Avvvnltv vv
`T Q ménrnnncnccre se nrficnnfn
`
`la méningite a méningocoque et la septice-
`niques:
`mie a méningocoque. La premiere forme est la plus
`commune, mais eiie répond bien au traitement. En
`revanche, 1a septicémie a méningocoque, moins fré-
`quente, est mortelle, méme quand elle est traitée acti-
`vement. La méningite a meningocoque est la seule
`forme qui provoque des épidémies. Celles-ci peuvent
`éclater dans n’importe quelle partie du monde;
`cependant,
`les plus grandes épidémies surviennent
`principalement dans la zone semi-aride de l’Afrique
`subsaharienne (“ceinture africaine dc la méningite”).
`En dehors des épidémies, la méningite a méningo-
`coque sévit sous forme de cas sporadiques dans
`lensemble du monde, avec des variations saison-
`niéres, et représente une part plus ou moins impor-
`tantes des méningites bactériennes endémiques.
`U11 Groupe de travail de l’OMS a récemment
`préparé un guide de 72 pages contenant des indica-
`tions pratiques pour la lutte contre les méningococ-
`eies, a l’intention des personnels de santé et des
`autorités sanitaires, a tous les niveaux.“ Ses cinq cha—
`pitres couvrent divers sujets dont les plus importants
`sont les suivants:
`
`" Lune contre les épidémies de méningite a méningocaque:
`guide pratique OMS. Lyon, Edition Fondation Marcel Mérieux,
`1995.
`
`554
`
`o Ampleur du proble‘me: revue des épidémies obser-
`vées depuis les années 70 (périodicité et variations
`saisonnieres des epidemics, caracte’ristiques des e’pi-
`démies); conditions favorisant les épidémies (séro-
`groupes et sérotypes,
`immunité, facteurs demogra-
`phiques); place de la méningite a méningocoque
`parmi
`les méningites bactériennes
`(méningite a
`méningocoque endémique, autres causes de meningi-
`te bactérienne).
`
`I‘nn MAnnnnnnnnnn
`[\nnlniun
`0 La maladie: comment reconnaitre et confirmer
`uIIU IIIUIIIIIEUVUUbIe (SYIllplullleS, exau-eu CIIIIIL‘uv,
`ponction lombaire et examen du liquide céphalo—
`rachidien (LCR), diagnostic différentiel); comment
`prendre en charge les maiades (traitement antibio-
`tique,
`traitement symptomatique, prise en charge
`simplifiée dans des conditions défavorables); com—
`ment prévenir les méningococcies (vaccination, chi-
`mioprophylaxie).r
`I‘
`v" 5"!» u “vow-(vow
`5. yvly
`vr‘ww” Gov WV
`nnnfi'rmgr "no pnulpmrp rip
`e Cnmmont (lamp or of
`1
`
`méningite d meningocoque. épidémie ou endémie?
`planification et mise en (euvre d’un systeme d’alerte
`précoce (coiiecte e‘t transmission de i‘information,
`analyse réguliere des données, comment determiner
`l’émergence d’une épidémie);
`evaluation rapide
`d’une alerte a l’épidémie (investigation des cas sus—
`pects).
`
`0 Comment nlanzf"er et gérer la réponse d une épi-
`démie. comité de crise national ou provincial; infor-
`.u-no
`1.2L
`Winn
`mation du public; organisation d’uneréponse urgente
`applupllée (vaCCulaliuu, blllllllUlJlUyllyldAlC, lllCDulCD
`générales);
`realisation ct suivi du programme de
`lutte; rappon sur l’épidémie.
`
`o Prophylaxie interépide’mique: prevention autour
`(1’ un cas de méningococcie, en dehors (1’ 1.1116 épidé-
`mie; vaccination de
`routine;
`réglementation et
`recommandations pour les voyageurs.
`
`L’ouvrage contient une liste de 84 references a
`des articies originaux et 10 annexes qui donnent des
`informations sur les points suivants:
`vvuuu
`w......... .m w"!
`_. rnlnrntinn (15 Gram et nnlnrqfinn m him
`méthyléne;
`
`—— test d’agglutination au latex;
`—— chloramphénicol injectable en solution huileuse;
`
`— laboratoires producteurs de vaccins;
`
`—— iogicieis informatiques destinés aux investiga—
`tions épidémiologiques;
`
`—— materiel nécessaire pour
`épidémie;
`n.“9
`~— matériels de laboratoire pour le diagnostic de
`Alma-awn mnnrnnrt;
`1
`”was“ m menu. um.
`
`l’investigation d’une
`
`—— preparation du milieu de transport Trans-isolate;
`
`WHO Bulletin OMS. Vol 73 1995
`
`(cid:19)(cid:19)(cid:19)(cid:19)(cid:19)(cid:26)
`000007
`
`AKER877ITCOO739753
`
`

`

`
`
`— foumisseurs de kits pour 1es campagnes de vacci-
`nation de masse;
`
`--— organisation d’unc carnpagne dc vaccination dc
`masse.
`a
`n “Ant on
`nub-l
`nrnr‘III-nr .m ovamnlnhm r‘n
`uu Pvu an kuuu
`1.11»: ull UAUIIIPXUIIV uv C8 51111.1.»
`en s’adressant au Dr E Tikhomirov, Division des
`Maladies transmissibles, Organisation mondiale de la
`Santé, 1211 Genéve 27, Suisse.
`
`été notables du fait que, pour la premiereesofois depuis
`__ .......
`14.1 JA..1‘
`1943, une flambée de fievreJaune a étéd0ccumentée
`au Kenya. U11 1111211
`1216 295 C33 0111 cu: use-ares a
`1 OMS en 1992, entralnant 102 déces, soit un taux de
`’11 AAA
`AA IA...“ 1A1’307\
`10.4,"...
`110,"...
`létalité de 35%. Ces chiffres comprennent 176 cas et
`1.1 1.16ch (La'uX uc 161(11119 14m; 611 [1111un 61 1 17 van
`et 81 déces (taux de létalité 68%) en Amérique du
`Sud. En 1993, cc sont 218 cas et 38 déces (taux de
`létalité 17%) qui ont été déclarés en Afrique, et 175
`cas entrainant 79 décés (taux de létalité 45%) en
`Amérique du Sud, totalisant 393 cas at 117 déces
`(taux de létalité 30%). On trouvera dans le tableau 1
`une récapitulation du nombre de cas de fievre jaune
`et de décés notifiés a l’OMS par ses Etats Membres
`pour la période de 1989 a 1993.
`
`Akmue
`
`11 y a eu par rapport aux armées précédentes une
`diminution spectaculaire du nombre de cas de fiévre
`jaune enregistrés, seuls 1e Kenya et le Nigeria en
`ayant déclaré en 1992; 1e Ghana a connu en 1993
`onn‘
`une petite flambée qui s’est poursuivie jusqu’en
`1534.
`
`Ghana. En 1993, une flambée de fievre jaune est sur—
`venue dans la région du Nord—Ouest, avec 39 cas et
`15 déces (taux de létalité 38%).”7 L’épidémie a débu-
`té en octobre 1993, et on continuait a enregistrer des
`cas en de’cembre. La transmission paraissait limitée
`au district de Jiripa. Le diagnostic de fievre jaune a
`été confirmé sérologiquement. Parmi les 37 cas 011
`Page et le sexe ont été signalés, 15 malades (40%)
`avaient moins de 15 ans, et 9 (24%) étaient de sexe
`fe’minin. Une campagne de vaccination a été entre-
`prise en décembre 1993 et poursuivie en 1994; elle
`semble avoir jugulé l’épidémie.
`
`
`
`’ D‘aprés: La fiévre jaune en 1992 et 1993. Relevé épidémiolo-
`gique habdamadalre. 1995. 70(10): 65—70.
`"' Fiévre iaune, Ghana. Relevé épidémio/ogique hebdomadaire,
`1994, 69(6): 44; at 1994, 69(10): 76.
`
`WHO Bulletin OMS. Vol 73 1995
`
`Notes et actlvltés OMS
`
`Kenya. La premiere flambée de fiévre jaune signalée
`au Kenya depuis 1943 a débuté en septembre 1992 et
`s’est poursuivie jusqu’en mars 1993. Elle s’est limi-
`tée aux districts de Baringo et d’Elgeyo Marakwet,
`___ a_a_1
`___ ___i __1 __a_..__
`dans la vallée de Kerio, au nord-ouest de Nairobi. On
`a erueg1stré au lULdJ 54 045 qui Ulll c1111a111é 20 déces
`(taux de létalité 52%). Dans 18 cas (33%),
`les
`malades avaient 19 ans ou moins, et 19 cas (35%)
`étaient de sexe féminin. Les conclusions de l’enquéte
`épidémiologique sont en faveur d’une flambée de
`fiévre jaune de brousse. Le virus a été isolé dans des
`échantillons cliniques prélevés sur des malades (cas
`mortels et non mortels) et sur des moustiques captu-
`rés. La caractérisation moléculaire des virus isolés
`
`montre une composition génétique similaire a celle
`de virus isolés chez l’homme et le moustique lors de
`précédentes epidemics de fibvre jaune en Afrique
`orientale, mais distincte de celle de virus provenant
`de specimens originaires d’Afrique occidentale ou
`d’Amérique du Sud. La flambée s’est arrétée a la
`suite d’une campagne de vaccination de masse
`durant laquelle pres d’un million de doses de vaccin
`antiamafil ont été administrées aux personnes rési-
`dant dans les zones 1 risque.
`
`i1 n’a été déclaré au Nigéria que
`Nigéria. En 1992,
`149 cas de fievre jaune et 8 de’ces (taux de létalité
`5%), contrairement a un passé récent oil 1es cas
`documentés se