- LAS PAUTAS ACELERADAS DE VACUNACIÓN NO SÓLO REPRESENTAN UN BENEFICIO PARA LOS VIAJEROS DE

ÚLTIMA HORA, SINO QUE FACILITAN EL CUMPLIMIENTO Y CONTRIBUYEN A ALCANZAR COBERTURAS MÁS

ELEVADAS -

Prevencion de la Malaria en el viajero

II Curso teorico- practico de

Actualizacion en Malaria.

Fundacion io- Hospital Carlos III

Mayo 2012

Contenido:

• Prevención de la malaria:

– Medidas anti-mosquito

– Profilaxis:

• ¿Por qué?

• ¿Con qué?

• ¿Cómo?

• ¿Cuándo?

• Autodiagnóstico y Autotratamiento.

Destino:: Angola Estancia : Intermitente Tipo de viaje: Trabajo. Auxiliar vuelo No profilaxis. Autotratamiento

Destino: Guinea Ecuatorial Duracion: Ilimitada Profillaxis: No

Destino: Senegal Duracion : 2 meses Profilaxis: Doxiciclina

Destino: Ghana Duracion: Ilimitada Profilaxis : No

Destino: Angola Duracion : 7 dias para volver despues 1 o 2 años- Profilaxis: Malarone solo el primer viaje

¿Dónde hay que prevenir la malaria?

– Listados de países con transmisión endémica:

• Carlos III

• OMS

• CDC

• NaTHNaC (National Travel Health Network and Centre. UK)

• Travax... // ...

¿Dónde hay que prevenir la malaria?

• Emplear listado de países con especificación de áreas + Atlas

• Emplear libros con mapas de países

• Emplear mapas de países en internet:

– Fit forTravel http://www.fitfortravel.nhs.uk/home.aspx

– Travax (UK, Scotland)

– Travax EnCompass (CDC)...

Malaria Endemic Areas

• Los paises endemicos se encuentran alrededor del cinturon del ecuador.. Muchos factores influyen en la transmision e intensidad.

Viajes y Malaria

Casos de Malaria importada

•Resto de Europa 6000 casos de malaria al año. • UK 2000 casos malaria /año • Alemania 1000 casos malaria/año • Francia 1000 casos malaria/año.

Un 50% de todos los casos son debidos a P. falciparum con mortalidad en 1%

Los casos de malaria mortal son: • No adherencia a quimioprofilaxis • Qumioprofilaxis inadecuada • Diagnostico medico tardio

Datasource: R Behrens, International passenger survey, unpublished data

Grado de transmision en areas geograficas

Zonas rurales y humedas de Africa del oeste tienen un riesgo de 10 a 100 veces mayor que zonas secas de Africa y Asia

La mayoria de casos de P. Falciparum ocurre en Africa Subsahariana , sobre todo en Africa del OesteMas del 6% de viajeros sin quimioprofilaxis adquieren malaria por més en Africa del oeste comparado con el 1% o menos en Africa del Este

RISK GROUPS

VFRs e Inmunidad Enfermedad severa y muerte en Malaria por P. falciparum. Lombardy, 1991 – 1995 (N=551)

Matteelli et.al., Trop Med Int. Health 1999; 4: 653

Datos del estudio de Matteelli et al demuestra que la mayoria de las muertes y casos graves de Malaria ocurren en viajeros no inmunes Datos similares se ven en otros estudios epidemiologicos Esto proporciona cierta evidencia de que la inmunidad proteje contra las formas severas (muerte y complicaciones) en individuos previamente inmunizados)

Viajeros de negocio

Los viajeros de negocio tienen mas riesgo de malaria grave debido a:

•Son avisados con muy poco tiempo y casi sin tiempo para consejo apropiado para el viaje •No son partidarios de tomar quimioprofilaxis, temen efectos adversos debido a profilaxis repetida o a tener que tomarla mucho tiempo • Buscan ayuda medica mas tarde

La mortalidad de malaria por P. falciparum en viajeros de negocio (25%) excede el total de casos de malaria por P. falciparum (7%)

Viajes de negocios Casos de Malaria importada por Plasmodium falciparum y mortalidad en UK desde Africa (1991-2000)

A pesar de tener una pequeña proporcion de casos de malaria, constituyen un desproporcionado numero de muertes

Tourism 57%

Cases N=10,920

VFR's 36%

Business 7 %

Fatalities N=91

Tourism 67 % Business 25%

VFR's 8%

Viajeros mayores

Aunque la edad por si misma no es una contraindicacion para el viaje, los viajeros mayores deben saber que tienen mas riesgo de :

1. Mas complicaciones de la malaria 2. 6 veces mas posibilidades de

mortalidad por malaria 3. Dificultad en la aclimatizacion. 4. Mas facilidad de accidentes 5. Complicaciones por patologia de

base. 6. 3 veces más frecuente la malaria

cerebral.

• mas vulnerable a adquirir infeciones en el viaje

Niños El riesgo mas alto lo tienen los niños VFRs que visitan familiares durante las vacaciones de verano. Tienen mas riesgo de malaria debido a: • Inmadurez del sistema inmune • Dificultad en administrar los antimalaricos • Dificultad en proteger de las picaduras de mosquito

Pregnant women

Pregnant women, particularly primigravidae, need to think carefully before travelling to a malarious area for a number of reasons:

if malaria is contracted, the clinical course is often more severe as the following complications may occur:

1. abortion and stillbirth 2. anaemia 3. low birth weight 4. higher peripheral parasitaemia 5. placental infection 6. fatality rates 3 times higher

prophylactic antimalarials may be contraindicated (doxycycline) or to be used with caution in pregnancy (malarone, mefloquine)

Adequate chemoprophylaxis, mosquito control measures and prompt treatment of symptomatic episodes are of paramount importance

HIV infected travellers As HIV has changed dramatically in terms of morbidity and mortality due to highly active antiretroviral therapy (HAART) many HIV infected individuals are now travelling to tropical and subtropical destinations.

In case of malaria infection, HIV infected individuals in comparison to non HIV infected individuals have:

• higher rates of parasitaemia • higher rates of clinical malaria • more severe disease

The risk of severe malaria depends on the

• HIV status and • pre-existing malaria immunity

This risk increases with a declining CD4 T-cell count, particularly with a count < 200mcl/L.

Expatriates/long term travellers Malaria is the leading cause of death among expatriates who died from infectious diseases and continues to pose a threat in sub-Saharan Africa, Papua New Guinea and Papua where the rate of malaria is at least 10-fold greater than in other malarious countries.

Length of stay often varies from months to years, long enough to necessitate some form of assimilation into the host environment.

Incidence of malaria in expatriates ranges from

• 31/1000 year in Asia to • 209/1000 per year in West Africa

Expats are at increased risk of malaria as:

• compliance to preventative measures declines over time • not all inividuals will report their illness • diagnosis is often made on symptoms without a confirmatory laboratory diagnosis • false positive malaria reports from laboratories in developing countries may be as high as 70%.

La piramide de la prevencion

B Bites:Medidas de proteccion personal

A Atencion: Ser conscientes del riesgo

C Cumplimiento: Quimioprofilaxis

D Diagnostico rapido y tratamiento rapido

Malaria prevention methods

¿Dónde hay que prevenir la Malaria?

• Hábitat del mosquito:

– Temperatura: 20ºC - 30ºC. No menos de 16ºC

– Humedad: final temporada de lluvias

– Altitud: < 1500 m (Hasta 2000 - 3000)

– Latitud: «del trópico de Cáncer al de Capricornio»

Prevención de la Malaria

– Conocer costumbres del mosquito:

• Activos durante el crepúsculo y el amanecer

• Nocturnos

• Hábitat: zonas húmedas

• Doméstico / peridoméstico / rural

Bite Prevention

Prevention consists of: a. Personal Protection Methods (PPMs)

•Insecticide Treated Bed Nets • Insecticide repellents • Protective Clothing • Coils • Screening Doors and Windows • Chemoprophylaxis (see next section)

b. Vector control methods (VCM)

•Space spraying

Bite Prevention

Insecticide treated nets (PPM)

Prevención de la Malaria: Prevención de las picaduras

• Necesaria a pesar de quimioprofilaxis

• Insecticidas:

– Sprays aéreos:

• Resultados inmediatos (brotes)

• Breve

• Resistencias

• Caros

Prevención de la Malaria: Prevención de las picaduras

– Sprays residuales: • Afecta a los insectos que se posan en paredes

• Útil en Anopheles

• Resistencias

• Caro

– Espirales: Piretroides (permetrina) • Riesgo incendio

• Preocupación por problemas de salud

• Más eficaz interior

– Vaporizadores: Reducen la entrada • Muy volátiles: escasa toxicidad.

Prevención de la Malaria: Prevención de las picaduras

• Ventiladores.

• Aire acondicionado

• Mallas en las ventanas / Puertas

Bite Prevention Insect repellents

Mosquitos are responsible for more than 700 million cases of insect born diseases annually, both in the tropical and subtropical as well as the more temperate zones around the world. Insect Repellents are a simple and important personal protection methods. In the case of malaria transmission, they have to be applied at dusk when the female anopheline mosquitos start to become active

Insect Repellents can be divided into two categories:

a) Synthetic Chemicals

b) Plant derived products

•DEET (N,N-diethyl-m-toluamide) • IR3535 (ethyl butylacetylaminoproprionate) • KBR305 (Piperidine)

• Citronella • Eucalyptus • Soybean-oil • Others (essential oils from cedar, eucalyptus, peppermint, lemongrass, geranium)

Bite Prevention Insect repellents

How do they work?

•Normally the anopheline mosquito is attracted directly by the smell of CO2 emission from the human host. • chemical receptors in their antennae direct them to humans. • Once within a centimetres of the human host, repellents interfere with the antennae receptors and prevent feeding.

Bite Prevention

Insect repellents

Synthetic Chemicals

DEET is the best available insect repellent presently available and has been in use since 1957. DEET is a broad spectrum repellent, effective against many species of mosquitos, biting flies, chiggers, fleas and ticks.

It is sold in a variety of formulations available from 5-100%. Generally, the higher the concentrations of DEET the longer protection will last. This mathematical relationship peaks at about 50% concentration, whereby any incremental dose of DEET concentration provides relatively little additional protection.

•10-40% DEET adequate for most activities • 50% DEET ideal dose if very good protection needed. • 100% DEET rarely ever needed (rain forest trips etc.)

Bite Prevention

Natural products

Insect repellents

Characteristics

These are normally single or blends of essential oils e.g.

Citronella (see the citronella lamp image) Eucalyptus Oil Eucalyptus (Lemon eucalyptus) and and a whole range of other less commonly used essential oils

The efficacy of natural products is not as good as DEET

The protection of essential oils tend to be short-lasting with protection from only minutes up to 2 hours

They are often poorly studied and can be mildly irritant to the skin.

Bite Prevention

Insect repellents

Natural products

Time for repellent to drop to 50% efficacy:

1. DEET 6-8 hours 2. Lemon eucalyptus 2-5 hours 3. Citronella 1-3 hours

Gel and cream form better than liquid in terms of length of effectiveness

from Keystone textbook of Travel Medicine

Prevención de la Malaria Prevención de las picaduras

• Lo que no sirve:

– Aceite de Geranio

– Ajo o levadura

– Aparatos de ultrasonido

– Otros aparatos electrónicos

– Vitamina B1

– Aceite del árbol del té

– Aceite de baño

– Hidratantes sin repelentes

Malaria prevention methods Guidelines for safe and effective use of insect repellents (adapted from EPA guidelines)

1 For casual use, choose a repellent with no more than 35% DEET though up to 50% DEET is acceptable. Repellents with the same percent DEET may be used in children, However not in small infants.

2 Use just enough repellent to lightly cover the skin, do no saturate the skin.

3 Repellents should be applied only to exposed skin and/or clothing -do not use under clothing.

4 For maximun effect apply to all exposed areas of skin.

5 To apply to the face, dispense into the palms, rub hands together, and then apply a thin layer to the face

6 Avoid contact with eyes and mouth- do not apply to children's hands to prevent possible subsequent contact with mucous membrane.

7 After applying, wipe repellent from the palmar surfaces to prevent inadvertent contact with the eyes, mouth, and genitals.

8 Never use repellents over cuts, wounds, inflamed, irritated or eczematous skin.

9 Do not inhale aerosol formulations or get in eyes.

10 Frequent reapplication is rarely necessary, unless the repellent seems to have lost its effectiveness. Reapplication may be necessary in very hot, wet environments, due to rapid loss of repellent from the skin surface.

11 Once inside, wash off treated areas with soap and water. Washing the repellent from the skin surface is particualrly important under circumstances where a repellent is likely to be applied for several consecutive days.

Prevención de la Malaria: Quimioprofilaxis

• Medicación que evitará el desarrollo de la enfermedad en su fase hemática.

• Sobre todo para p. falciparum

• Selección del fármaco según: – Zona, Resistencia a Cloroquina

– Tipo de viaje

– Duración

– Antecedentes del viajero

Chemoprophylaxis

. Decidir un quimioprofilactico u otro en funcion de:

• Eficacia

• Tolerancia

• Complicaciones

• Coste

• Condiciones medicas preexistentes

• Modo de accion

Liver - stage prophylaxis

Blood - stage prophylaxis

Malaria - Life cycle

0 7 < 30 > 60 Days

Malaria prophylaxis, by site of action

Clinical infection Exposure

Recordando ciclo del Parásito

Picadura de

Mosquito.

♀

anopheles

Entrada de

Esporozoítos

en torrente

circulatorio

Captación

por el

hígado

Formas

“durmientes”

Hepáticas.

Sólo en p.

ovale y p.

vivax

Desarrollo

intrahepático

de todas las

especies de

parásitos.

Esquizonte.

Ruptura de los

hematíes y salida

de merozoítos.

Invasión de otros

hematíes.

Desarrollo como

gametocitos.

Salida de las

formas hepáticas

durmientes.

(Meses tras la

entrada)

Salida a la

circulación e

invasión de los

hematíes.

Merozoítos.

Profilaxis de Supresión

Profilaxis causal

Prevención de

picaduras de

insecto

Gametocitos recogidos por la

picadura de hembra de

Anopheles. Completan el ciclo

en el mosquito convirtiéndose

en esporozoítos.

Quimioprofilaxis: Las tres grandes

Mefloquine Doxycycline Atovaquone- proguanil

Y para zonas cloroquin-sensibles….

Quimioprofilaxis con Cloroquina

• Primera elección en zonas con p.falciparum no resistente

• Profilaxis supresiva:

– Continuar un mes al salir de zona de riesgo

Quimioprofilaxis con Cloroquina

• Sí activa frente a p. malariae, ovale y vivax (excepto en Indonesia Timor Oriental, Papúa Nueva Guinea, Etiopía...)

• NO actúa frente a formas latentes hepáticas

Quimioprofilaxis con Cloroquina

• Seguro, administración semanal

• Precauciones:

– Epilepsia

– M. Gravis

– Psoriasis

– Fármacos antiarrítmicos

– Tratamiento prolongado

– Antagoniza vacuna de Rabia (solo si se usa via intradermica)

Quimioprofilaxis Mefloquina

• Profilaxis supresiva

• Administración semanal

• Ventajas: – Uso prolongado

– Seguro

• Efectos adversos: – Neuropsiquiátricos (pilotos y submarinistas)

– Interacciones con fármacos cardiológicos

Quimioprofilaxis con Atovaquona-Proguanil

• Profilaxis causal

– Sólo una semana al retornar.

• Seguro, escasos efectos adversos:

– Digestivos (menores)

– Aftas orales

• Limitación de tiempo ?

Quimioprofilaxis: Tetraciclinas

• Doxiciclina

• Profilaxis supresiva

• Efectos adversos – Digestivos: reflujo, esofagitis

– Fotosensibilidad

– Micosis

• Interacciones con: – ACO

– Antiácidos

Quimioprofilaxis: Cloroquina + Proguanil (Savarine)

• Prácticamente no se emplea:

– Sólo indicado en: Nepal, Sri Lanka y Tajistan y en zonas de Colombia. en India.

– Seguro en embarazadas

Quimioprofilaxis: Primaquina

• No se emplea habitualmente

• Profilaxis terminal para P. Ovale y P. Vivax.

• ¿Profilaxis causal?

• Determinar siempre G6PD

Malaria Prophylaxis Long term use

Specific UK guidelines on malaria prophylaxis for longterm travellers are written by the Health Protection Agency’s Advisory Committee for Malaria Prevention (ACMP) and have been last revised in 2006. These guidelines apply to individuals who are travelling through or visiting malaria endemic countries for over 6 months. Long term travellers are at even greater risk of acquiring malaria than short term travellers as the “cumulative risk of contracting malaria is proportional to the length of stay in a malarious country”. For example, a 3 month visit to a malarious area carries a six times greater risk than a visit of two weeks. This is nicely demonstrated by the graph. It shows furthermore, that the risk of adverse events from chemoprophylaxis stabilises over time. This implies that effective antimalarial use is even more important for long term travellers than short term travellers.

Cumulative risk of adverse events and of malaria

Prophylactic Agents

Long term use

The following table summarises the various chemo prophylactic agents used for long term travellers and indicates their maximum licensed use

Time restrictions may be conservative due to lack of safety data for long term use. In the case of Atovaquone and Proguanil, this drug is now increasingly used for much longer periods of time.

Chemoprophylactic agents

Chloroquine + Proguanil as long as appropriate

Doxycyline < = 2Years

Atovaquone & proguanil 3~6 months (USA no restriction)

Mefloquine < = 3 years

Reactions to Antimalarials Adverse Events

Adverse reactions to antimalarials tend to occur most often after the first dose for rapidly excreted drugs and after one of the first few doses for drugs that are excreted more slowly.

Travellers are advised to start taking antimalarials up to three weeks before travel in order to have protective blood levels at the time of travel and equally important to assess any adverse events.

More than 75% of all adverse events in the case of Mefloquine manifest within the first three weeks of travel and therefore allow switching to an alternative antimalarial agent. For most agents adverse effects tend to become less frequent over time whilst the risk of malaria is a cumulative one.

Overall the prevalence of adverse reactions and of discontinuing chemoprophylaxis because of them is roughly comparable between regimens as the figure shows.

Drug associated adverse events in 21% of travellers

Hogh et.al. Lancet 2000

Prophylaxis Users

Adverse Events

Proportion of prophylaxis users reporting mild to moderate adverse events by prophylaxis regimens. This graph details neuropsychiatric and gastrointestinal events only. Mefloquine has a relatively higher frequency of neuropsychiatric events, the largest proportion are sleep disturbances. The subjects were blinded to the regimen they were taking.

RELATIVE FREQUENCY OF ADVERSE EVENTS EVENTS BY REGIMEN

Resistance development

Chloroquine and Proguanil:

Chloroquine-resistant P.falciparum (CRPF) is now widespread in many malaria endemic countries orldwide (see map below) with the exception of;

•Mexico, the Caribbean, Central America, Argentina • parts of the Middle East and China

Chloroquine-resistant Plasmodium vivax is also a growing problem and affects areas in:

Papua New Guinea, West Papua (Irian Jaya), Vanuatu, Myanmar Guyana

Global Resistance 2006 Resistance of Plasmodium falciparum to:

Chloroquine occurred first in Colombia and Thailand in 1960’s and spread to Africa. Today, only north of the Panama Canal have no chloroquine-resistant P. Falciparum malaria.

Mefloquine is found mostly in Cambodia, Myanmar, Thailand and Vietnam.

Artemisinin or artemisinin derivatives. No resistance

Atovaquone /proguanil. Occasional failures of treatment are reported.

Diagnosis Early diagnosis and prompt treatment aims at “preventing” severe morbidity and mortality of malaria rather than infection itself. Untreated, Falciparum malaria can progress rapidly from just a febrile to a severe life threatening infection with very serious complications and in the worst case not uncommonly leads to death

The mainstay of effective disease management is:

•Recognition of possible malaria symptoms •Early and correct diagnosis of malaria prompt treatment with the correct dose of an effective antimalarial •Completion of treatment ensure:

• clinical or parasitological cure • prevent selection of drug resistance • interrupt transmission in low endemicity areas

For the traveller it is of particular importance to think of “malaria” when in a malaria endemic area. As “non-immunes” the clinical course can progress rapidly.

AUTODIAGNOSTICO

POR LA CLINICA:Toda fiebre que aparezca pasados los seis o siete días de estancia en zona de riesgo puede ser malaria mientras no se demuestre lo contrario. La fiebre suele ser de >38º acompañada de malestar cefalea mialgia escalofríos y sintomas gastrointestinales.

POR TEST DIAGNOSTICOS: Detectan mediante inmunocromatografia antígenos en sangre de P. Falciparum y P. Vivax. Por falta de practica para realizarlo se obtienen falsos negativos.

Early Diagnosis and Prompt Treatment

In the absence of prompt access to good medical facilities in case of a proven or suspected malaria diagnosis, Standby Emergency Treatment should be considered, especially for those who:

• will be unable to get medical advice within 24 hours of becoming ill • have access to advice but are in places where suitable drugs are unavailable • will be travelling for periods greater than one month For effective and safe use by for travellers; • clear written instructions on use should be issued • after use of treatment, medical advice should be sought as soon as possible • standby therapy should be recommended as soon as malaria is suspected, ideally with laboratory confirmation

The following are symptoms that should alert the traveller to the possibility of malaria:

•flu symptoms • fever • diarrhoea • joint pains

Standby Emergency Therapy The following regimens may be used as standby treatment in adults

Advantages: Correct drugs available and good quality. Used with training and a diagnostic kit. Disadvantages: May be used for an inappropriate disease and lead to a more serious problem. Breakthrough malaria is rare when chemoprophylaxis is used relatively compliantly.

Co-artemether (Riamet)

20 mg artemether plus 120 mg lumefantrine 24 tablets over 60 hours

Chloroquine Multi-drug resistant falciparum malaria

Atovaquone plus Proguanil

250 mg plus 100 mg 3 tablets day for 4 days

Chloroquine Multi-drug resistant falciparum malaria

Quinine plus Doxycycline

600 mg quinine TDS and100 mg doxycycline daily for 7days

Chloroquine Multi-drug resistant falciparum malaria

Quinine plus Clindamycin

600mg quinine TDS and 450mg clindamycin TDS for 5-7 days

Pregnancy

Casos especiales

• Epilépticos: No deben tomar ni cloroquina ni mefloquina .

• Personas que desarrollen trabajos de precisión: No deben tomar la mefloquina

• Insuficiencia renal: Los anti-maláricos más seguros son la mefloquina y la doxiciclina

• Porfiria: no dar Fansidar, doxiciclina, atovacuona/proguanil

• La cloroquina y el proguanil son relativamente seguras durante el embarazo y lactancia son las drogas indicadas para la profilaxis, caso tenga que viajar para una zona endémica de malaria. Si toma proguanil, debe tomar un suplemento de ácido fólico diario.

• Estancias prolongadas……

Muchas

Gracias

Mlago.hciii

@salud.madrid.org