W.F.Hui — Issues Related to Antivenom Distribution And

WHO CONSULTATIVE MEETING RABIES AND ENVENOMINGS: A NEGLECTED PUBLIC HEALTH ISSUE

ISSUES RELATED TO ANTIVENOM DISTRIBUTION AND APPROPRIATE USE

Hui Wen Fan Coordination of Anthropozoonosis Secretariat of Health Surveillance Brazilian Ministry of Health [email protected]

Geneva, 10th January 2007 BRAZIL: GENERAL INFORMATION

8,547,403.5 km2

169,799,170 population

27 states

5,567 municipalities

80% living in urban areas HISTORY

• 1901: Production of snake antivenoms in Brazil

• 1970’s decade: National Program for Self-Sufficiency in Biological Products

• 1986: National Program for Snakebites Control

• 2006: Four public manufacturers, nine types of antivenoms SURVEILLANCE PROGRAM FOR RABIES AND ENVENOMINGS CONTROL

ANTIVENOM PRODUCTION

INFORMATION ANTIVENOM SYSTEM DISTRIBUTION

EDUCATIONAL ANTIVENOM ACTIVITIES USE SURVEILLANCE PROGRAM FOR RABIES AND ENVENOMINGS CONTROL

INFORMATION SYSTEM

ENVENOMINGS BY POISONOUS ANIMALS IN BRAZIL, 1987-2005

100000 snake bites scorpion stings spider bites

80000

60000 nº cases nº 40000

20000

0 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 FIGURES OF ENVENOMINGS CAUSED BY POISONOUS ANIMALS BRAZIL, 2005

28,711 snake bites 36,558 scorpion stings 19,634 spider bites 15 cases/100,000 pop 16 cases/100,000 pop 10 cases/100,000 pop 114 deaths (0.40%) 50 deaths (0.14%) 9 deaths (0.05%) 200 HUMAN RABIES IN BRAZIL, 1980-2005 180

160

140

120

100

0 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 Casos 173 139 127 103 88 53 39 57 36 58 73 70 60 50 22 31 25 25 29 26 26 21 10 17 30 44 SURVEILLANCE PROGRAM FOR RABIES AND ENVENOMINGS CONTROL

ANTIVENOM PRODUCTION

INFORMATION SYSTEM ANTIVENOMS MANUFACTURERS IN BRAZIL

270,000 ampoules

190,000 ampoules

58,000 ampoules

6,000 ampoules Bothrops AV Crotalus AV Bothrops-Crotalus AV Bothrops-Lachesis AV Coral (Micrurus) AV Tityus scorpion AV Arachnidae AV (Tityus, Phoneutria, Loxosceles) Loxosceles AV Lonomia caterpillar AV

Rabies AV SURVEILLANCE PROGRAM FOR RABIES AND ENVENOMINGS CONTROL

ANTIVENOM PRODUCTION

INFORMATION ANTIVENOM SYSTEM DISTRIBUTION Principles for a rational distribution

• Based on epidemiological data – Season variation – Geographical distribution

• Decentralized – Nº health centres as much as possible – Access to treatment as soon as possible (< 6 hrs)

• According to manufactory conditions – Transport / Storage ANTIVENOM MENSAL DISTRIBUTION AND UTILISATION. Brazil, 2004

40.000

35.000

30.000

25.000

20.000 nº ampoules nº 15.000

10.000

5.000

Jan Feb Mar Apr Maydistributed Junused Jul Aug Sept Oct Nov Dec ANTIVENOM MENSAL DISTRIBUTION AND UTILISATION. 35000 Brazil, 2005

30000

25000

20000

15000 nºampoules

10000

5000

0 jan feb mar apr may jun jul aug sep oct nov dec

used distributed Distribution of Lachesis muta (bushmaster) snake bites and specific antivenom to be distributed in Brazil, 2005.

A. Melgarejo. Alagoas, Brazil

Gil Patrick.La Paz, Bolivia HIERARCHY AND RESPONSABILITIES CONCERNING AV DISTRIBUTION

AV manufacturers

1 central level

27 regional levels (States)

3,156 local levels (municipalities)

3,208 Health centres for AV use 33 km between health units 32% of municipalites with AV

Health with centre AV

0 1 . 1 89 km between health units 100% of municipalites with AV CASE-FATALITY RATE OF SNAKE BITES ACCORDING TO TIME BETWEEN ACCIDENT AND AV TREATMENT Brazil, 2005

4,50 * 4,00

3,50

3,00

2,50 2,00 * * 1,50

1,00

0,50

0,00 <1 hr 1-3 hrs 3-6 hrs 6-12 hrs ≥12 hrs

pit viper SA rattlesnake bushmaster *p< 0,001

Source: Brazilian Information System of Diseases Conditions of transport and storage PLANNING ANTIVENOM DISTRIBUTION

Antivenom supply = [(cases x mean ampoules) + (stock – remaning)]

Cases: number of accidents previewed for a given period, e.g., one month

Mean ampoules: weighted number of ampoules used, considering severity of envenoming

Stock: strategic quantity of antivenom that should be available in case of unexpected increase or sub register of accidents, losses of AV (misuse, expiring date, storage and handle conditions) and deviations.

Remaining: number of ampoules not used in the previous period COST OF AV ACQUIRED BY BRAZILIAN MINISTRY OF HEALTH - 2005

US$ 8,548,595.27 466,760 ampoules ≡ or € 6,580,904.54 SURVEILLANCE PROGRAM FOR RABIES AND ENVENOMINGS CONTROL

ANTIVENOM PRODUCTION

INFORMATION ANTIVENOM SYSTEM DISTRIBUTION

ANTIVENOM USE PRINCIPLES OF ANTIVENOM THERAPY

• Precociousness in antivenom therapy

• Specificity of antivenoms

• Diagnosis of envenoming based on clinical and VITAL BRAZIL epidemiological features 1865-1950 – Geographical distribution of animals – Venoms actions / Local and systemic aspects of envenomings

• Amount of AV based on severity of envenoming ANTIVENOM MISUSE FOR SNAKE BITES IN BRAZIL, 2001-5

Bothrops Lachesis Crotalus Elapidae-Micrurus (lanced-head pit viper) (bushmaster) (S. A. rattlesnake) (coral snake) SAB, SABL, SABC SABL SAC, SABC SAEL

Type of envenoming total misused % Bothrops 568,529 8,915 1,57 Crotalus 91,270 9,275 10,16 US$ 533,812.46 Elapidae 3,881 1,152 29,68 € 410,941.07 Lachesis 16,028 8,280 51,66 Non poisonous 1,129 1,129 100,00 Total 680,837 28,751 4,22 Bothrops (lanced-head pit viper) snake bites: amount of antivenom recommended and administered. Brazil, 2005

Severity Rule Given Mean Min-Max

Mild 2-4 5.1 1-16

Moderate 4-8 7.1 2-18

Severe 8-12 10.5 2-50 Crotalus durissus (South American rattlesnake) snake bites: amount of antivenom recommended and administered. Brazil, 2005

Severity Rule Given Mean Min-Max Mild 55.8 1-20

Moderate 10 8.3 2-30

Severe 20 13.8 4-50 SURVEILLANCE PROGRAM FOR RABIES AND ENVENOMINGS CONTROL

ANTIVENOM PRODUCTION

INFORMATION ANTIVENOM SYSTEM DISTRIBUTION

EDUCATIONAL ANTIVENOM ACTIVITIES USE

For the success of rabies and envenomings surveillance program there are necessary:

• An information system that gives reliable figures; • Antivenoms of good quality and sufficient amount; • Rational logistics of antivenom distribution; • Continuous monitoring antivenom use and medical assistance; • Efficient education activities to reduce the impact of diseases as public health problems and thus antivenoms requirements. Bothrops alternatus