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PPT on Malaria

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Malaria :

Malaria Dr.D.Shankar Reddy Assistant Professor S.V.Medical College, Tirupati

World Malaria Day, April 25 :

World Malaria Day, April 25 April 25 is World Malaria Day, which commemorates the date in 2000 when 44 African leaders committed to cutting malaria deaths in half by 2010.

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The term malaria originates from Italian: mala aria — “ bad air” The disease was formerly called ague or marsh fever due to its association with swamps.

History – Events on Malaria:

History – Events on Malaria 1880 - Charles Louis Alphose Lavern discovered malarial parasite in wet mount 1883 - Methylene blue stain - Marchafava 1891 - Polychrome stain- Romanowsky 1898 - Roland Ross - Life cycle of parasite transmission, wins Nobel Prize in 1902 1948 - Site of Exoerythrocytic development in Liver by Shortt and Garnham

Charles Louis Alphonse Laveran,:

Charles Louis Alphonse Laveran , Charles Louis Alphonse Laveran, a French army surgeon stationed in Constantine, Algeria, was the first to notice parasites in the blood of a patient suffering from malaria. This occurred on the 6th of November 1880. For his discovery, Laveran was awarded the Nobel Prize in 1907.

Ronald Ross:

Ronald Ross In August 20th, 1897, Ronald Ross, a British officer in the Indian Medical Service, was the first to demonstrate that malaria parasites could be transmitted from infected patients to mosquitoes For his discovery, Ross was awarded the Nobel Prize in 1902

Major Developments in 20th Century:

Major Developments in 20 th Century 1955 - WHO - world wide malaria eradication programme using DDT. 1970 – Mosquitos developed resistance to DDT, Programme fails. 1976 – Trager and Jensen in vitro cultivation of parasite

MAJOR MALARIA ECOTYPES FOUND IN INDIA:

MAJOR MALARIA ECOTYPES FOUND IN INDIA TRIBAL MALARIA RURAL MALARIA URBAN MALARIA PROJECT MALARIA BORDER MALARIA

EPIDEMIOLOGICAL DETERMINANTS:

EPIDEMIOLOGICAL DETERMINANTS

AGENT FACTORS:

AGENT FACTORS AGENTS LIFE CYCLE INCUBATION PERIOD RESERVOIR OF INFECTION PERIOD OF INFECTIVITY

AGENT: HUMAN MALARIA PARASITES:

AGENT: HUMAN MALARIA PARASITES Plasmodium vivax Plasmodium falciparum Plasmodium malariae Plasmodium ovale

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Exo- erythrocytic (hepatic) cycle Sporozoites Mosquito Salivary Gland Malaria Life Cycle Life Cycle Gametocytes Oocyst Erythrocytic Cycle Zygote Schizogony Sporogony Hypnozoites (for P. vivax and P. ovale )

INCUBATION PERIOD :

INCUBATION PERIOD 12 (9-14) days for Falciparum malaria, 14 (8-17) days for Vivax malaria, 28 (1.8-40) days for Quartan malaria and 17 (16-18) days for O vale malaria

RESERVOIR OF INFECTION :

RESERVOIR OF INFECTION P malariae , no other animal reservoir of human plasmodia is known to exist A human reservoir harbours the sexual forms (gametocytes) of the parasite. A patient can be a carrier of several plasmodial species at the same time. children are more likely to be gametocyte carriers than adults.

PERIOD OF INFECTIVITY :

PERIOD OF INFECTIVITY gametocytes are infective to mosquito Vivax infections, gametocytes appear in blood 4-5 days Falciparum infections, they appear after 10-12 days following asexual stage Gametocytes are the most numerous in early stages of the infection when their density may exceed 1,000 per cubic mm of blood.

RELAPSES:

RELAPSES It is usual for vivax and ovale malaria to relapse more than 3 years after the patient's first attack. Recurrences of falciparum malaria usually disappear within l-2 years. P. malariae has a tendency to cause prolonged low-level, asymptomatic parasitaemia . The infection is known to persist for 40 years or more.

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It is now considered more likely that vivax and ovale relapses are derived from original, sporozoite -induced, liver schizonts which have been latent long before bursting. In P falciparum and P malariae infections latent liver schizonts do not appear to occur.

HOST FACTORS :

HOST FACTORS AGE SEX RACE PREGNANCY OCCUPATION SCOCIO-ECONOMIC DEVELEPMENT HOUSING POPULATION MOBILITY IMMUNITY

AGE :

AGE Malaria affects all ages. Newborn infants have considerable resistance to infection with P falciparum . SEX Males are more frequently exposed to the risk of acquiring malaria.

RACE :

RACE Individuals with sickle-cell trait have a milder illness with falciparum Persons with “Duffy negative” RBC are resistant to P vivax infection. PREGNANCY Pregnancy increases the risk of malaria in women.

OCCUPATION :

OCCUPATION Malaria is related to agricultural practices . SOCIO-ECONOMIC DEVELOPMENT It is generally accepted that malaria has disappeared from most developed countries as a result of socio-economic development.

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HOUSING The ill-ventilated and ill-lighted houses provide ideal indoor resting places for mosquitoes. POPULATION MOBILITY Migration can occur within the country or out of country This process may import malaria

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HUMAN HABITS Habits such as Sleeping outdoors Nomadism refusal to accept spraying of houses replastering of walls after spraying not using measures of personal protection influence man-vector contact. IMMUNITY The epidemic malaria is influenced by the immune status of the population

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Infants born to immune mothers are generally protected during 3 to 5months by maternal IgG antibody. Active immunity is species-specific. People living in endemic exposed continually to malaria develop considerable resistance to clinical disease.

ENVIRONMENTAL FACTORS:

ENVIRONMENTAL FACTORS SEASON TEMPERATURE HUMIDITY ALTITUDE RAINFALL MAN-MADE MALARIA

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SEASON Malaria is a seasonal disease. In most parts of India, the maximum prevalence is from July to November. TEMPERATURE Temperature affects the life cycle of malaria parasite. The optimum temperature for development of the malaria parasite in the insect vector between 20 deg. to 30 deg.C

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HUMIDITY The humidity has effect on the length of life of the mosquito. A humidity of 60% considered necessary for mosquitoes to live their normal span of life. When the humidity is high,mosquitoes are more active and they feed more voraciously. ALITITUDE As a rule, Anophelines are not found at altitudes above 2000-2500 m.

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RAINFALL Rain general provides opportunities for the breeding of mosquitoes Rain increases atmospheric humidity Heavy rain may flush out the breeding places.

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MAN-MADE MALARIA Burrow pits, Garden pools, Irrigation channels and Engineering projects led to the breeding of mosquitoes and an increase in malaria.

VECTOR OF MALARIA:

VECTOR OF MALARIA DENSITY LIFE SPAN CHOICE OF HOST RESTING HABITS TIME OF BITING BREEDING HABITS VECTORIAL CAPACITY RESISTANCE TO INSECTICIDES

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Out of about 45 species of anopheline mosquitoes in India. An. culicifacies , An. fluvalitis , An. stephensi , an. minimus , An. philippinensis , An. sundaicus , and An. maculatus . The vectors of major importance are An. culicifacies in rural areas and An. Stephensi in urban India.

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DENSITY To be an effective vector, a species must be present in adequate density A sudden increase in density of vectors, may cause epidemic outbreaks. “critical density” below which effective transmission cannot be maintained in a community. An. Culicifacies -high density An.fluviatilis - lower density

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LIFE SPAN The vector mosquito must live for at least 10-12 days after an infective blood meal to become infective. The strategy in malaria eradication is to shorten the life span of mosquitoes to less than 10 days by insecticides.

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CHOICE OF HOST Some mosquitoes prefer human blood, some animal blood, and some show great variation in their feeding habits. The percentage of human blood feeds in the case of An.culicifacies , an important vector in India, has been found to from 2-80% An. fluviatilis is a anthrophilic species.

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RESTING HABITS After a blood meal, some mosquitoes rest indoors on the walls for quite sometime. This behavior pattern is know as " endophily ". But there are some species which rest outdoors ( exophily ). In fact, the concept malaria eradication is based on endophilism (indoor resting habits) of most malarial vectors. TIME OF BITING The majority of Indian mosquitoes bite at night excepting the Aedes mosquitoes..

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BREEDING HABITS Some breed in flowing water (An. fluviatilis ) brackish water ( An.sundaicus ) wells, cisterns, fountains and overhead tanks (An. stephensi ). VECTORIAL CAPACITY Capacity refers to the combined density of the vector population, its susceptibility to infection,life span,probability of feeding on man

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RESISTANCE TO INSECTICIDES On this depends on choice of insecticides to be used.

MODE OF TRANSMISSION:

MODE OF TRANSMISSION VECTOR TRANSMISSION DIRECT TRANSMISSION CONGENITAL MALARIA

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VECTOR TRANSMISSION Malaria is transmitted by the bite of certain species of infected, female anopheline mosquitoes. The mosquito is not infective unless the sporozoites are present in its salivary glands. A single infected vector, during her life time, may infect several persons.

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DIRECT TRANSMISSION Malaria may be induced accidentally by hypodermic intramuscular and intravenous injections of blood or plasma, eg ., blood transfusion, malaria in drug addicts . Blood transfusion poses a problem because the parasites keep their infective activity during at least 14 days in blood bottles stored at -4 deg.C .

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Persons who have lived in an endemic area (including those who have been taking anti malarials prophylactically ) and anyone who has had malaria should not be accepted as blood donor until 3 years . CONGENITAL MALARIA Congenital infection of the newborn from an infected mother may also occur - RARE

Laboratory Diagnosis of Malaria:

Laboratory Diagnosis of Malaria

Diagnostic Tools for Human Infections with Malaria:

Diagnostic Tools for Human Infections with Malaria Blood film examination Serology - IFA PCR

Appearance of Thick and Thin Smears:

Appearance of Thick and Thin Smears

QBC system has evolved as rapid and precise method in Diagnosis:

QBC system has evolved as rapid and precise method in Diagnosis The QBC Malaria method is the simplest and most sensitive method for diagnosing the following diseases. Malaria Babesiosis Trypanosomiasis ( Chagas disease, Sleeping Sickness) Filariasis (Elephantiasis, Loa-Loa) Relapsing Fever ( Borreliosis )

QBC system:

QBC system

Appearance of Malarial parasite in QBC system:

Appearance of Malarial parasite in QBC system

Serology:

Serology Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past experience.

Newer Diagnostic methods:

Newer Diagnostic methods Molecular Diagnosis Parasite nucleic acids are detected using polymerase chain reaction (PCR). This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory (even though technical advances will likely result in field-operated PCR machines).

Sensitivity of Tools for Diagnosis of Malarial Infection:

Sensitivity of Tools for Diagnosis of Malarial Infection Most sensitive: Antibody detection 2. PCR 3. Blood film examination

Measurement of Malaria:

Measurement of Malaria PRE ERADICATION ERA SPLEEN RATE : % of children B/W 2and10 years showing enlarged spleen Used for measuring endemicity AVG ENLARGED SPLEEN :refined spleen rate denoting avg enlargement of spleen PARSITE RATE : % of children B/W 2and10 years showing malaria parasite in blood film

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INFANT PARASITE RATE :% of infants showing malaria parasite In blood film Senstive index of recent malaria transmission in a locality If infant parasite rate is zero for 3 consecutive years in a locality ,it is taken as absence of malaria transmission

ERADICATION ERA ::

ERADICATION ERA : a. Annual parasite incidence (API) b. Annual blood examination rate (ABER) c. Annual falciparum incidence (AFI) d. Slide positivity rate (SPR) e. Slide falciparum rate (SFR).

Annual parasite incidence (API):

Annual parasite incidence (API) API is given by the formula : API = Confirmed cases during one year x 1000 Population under surveillance API is a sophisticated measure of malaria incidence in a community. It is based on intensive active and passive surveillance, and cases are confirmed by blood examination.

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ABER= No. of blood smears collected during the year x 100 Population covered under surveillance MBER= No. of blood smears collected during the month x 100 Population covered under surveillance INDEX OF OPERATIONAL EFFICIENCY

Slide Positivity Rate (SPR)::

Slide Positivity Rate (SPR): The Slide Positivity Rate among the blood smears collected through both active and passive surveillance gives a more accurate information on distribution of malaria infection in the community over a period of time. Monthly SPR can be calculated to find out the seasonal rise and fall in malaria prevalence in the community. SPR among children 2-9 years of age can be utilized for comparison with pre-control Child Parasite Rates to assess the impact of control measures on local malaria endemicity and transmission

SPR=No. of blood smears found positive for malaria parasite X 100 No. of blood smears examined :

SPR= No. of blood smears found positive for malaria parasite X 100 No. of blood smears examined Trends in SPR can be utilized for predicting epidemic situations in the area. If monthly SPR exceeds by 2 ½ times of the standard deviation observed in SPR of the preceding 3 years or preceding 3 months of the same year, an epidemic build up in the area can be suspected. Monthly or yearly trends of SPR are utilized to study the impact of control operations.

VECTOR INDICES:

VECTOR INDICES HUMAN BLOOD INDEX : proportion of freshly fed female anopheline mosquito whose stomach contains human blood Indicates degree of anthrophilism SPROZOITE RATE: % of female anophelines with SPROZOITE in their salivary glands

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MOSQUITO DENSITY: number of mosquitos per man hour catch MAN BITING RATE : avg incidence of anopheline bites per day per person

APPROACHES TO MALARIA CONTROL:

APPROACHES TO MALARIA CONTROL Two approaches Management of cases in the community Active intervention to control or interrupt malaria transmission

GUIDELINES for diagnosis & treatment:

Reduction in morbidity & mortality is the 1 st priority. National drug policy on malaria, 2009 The emphasis is on complete treatment in diagnosed cases rather than 1 single dose presumptive treatment to suspected cases to avoid chloroquine resistance in P. falciparum . All fever cases should be investigated for malaria by Microscopy or Rapid diagnostic kits. 61 GUIDELINES for diagnosis & treatment

Treatment of uncomplicated Malaria:

Confirmed P. vivax cases : Chloroquine in full therapeutic dose of 25 mg/kg body wt divided over 3 days. + Primaquine – 0.25 mg/kg body wt daily for 14 days under medical supervision, to prevent relapse ( Primaquine is contraindicated in G6PD deficient patients, infants & pregnant women, because of hemolysis ) 62 Treatment of uncomplicated Malaria

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Relapse rate in vivax malaria is around 30% in India,due to the presence of hypnozoites in liver. For its prevention , primaquine is given. Stop primaquine immediately if symptoms like Dark coloured urine, Yellow conjunctiva, Bluish discoloration of lips, Abdominal pain, Nausea, Vomiting , etc. occur

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Treatment of P. falciparum cases – - based on areas identified as chloroquine resistant/sensitive In confirmed cases of P. falciparum (sensitive) Chloroquine @ 25 mg/kg for 3 days + Primaquine @ 0.75 mg/kg on 1 st day In chloroquine resistant P. falciparum Artemisinin combination therapy (ACT) should be given ( Artesunate + Sulfadoxine – Pyrimethamine ) 64

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ACT consists of an artemisinin derivative combined with a long acting antimalarial like amodiaquine,lumefantrine,mefloquine or sulfadoxine-pyrimethamine . The ACT used in the national programme in India is - Artesunate + Sulfadoxine – Pyrimethamine . Artemether + Lumefantrine & Artesunate + Mefloquine , are also available.

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Artemisinin derivatives must never be administered as monotherapy ,as they can lead to development of parasite resistance.

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Treatment of uncomplicated P.falciparum cases in pregnancy- 1st trimester : quinine - 10mg/kg 3 times daily for 7 days . 2nd & 3rd trimester : ACT for 7 days .

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AREAS WHICH QUALIFY FOR ACT : Listed areas with high P.falciparum endemicity – Seven North-Eastern states, Andhra Pradesh, Chattisgarh , Jharkhand, M P & Orissa. Total 117 districts have been identified for ACT.

Treatment of mixed infections:

Mixed infections – Should be treated as Falciparum malaria 69 Treatment of mixed infections

MANAGEMENT OF CASES:

MANAGEMENT OF CASES Treatment schedule for uncomplicated malaria CHLOROQUINE (150mg base) 70 Age in years Day 1(10mg/kg) Day 2(10mg/kg) Day 3(5mg/kg) <1 ½ ½ ¼ 1-4 1 1 ½ 5-8 2 2 1 9-14 3 3 1 ½ 15 & above 4 4 2

MANAGEMENT OF CASES:

MANAGEMENT OF CASES 2. PRIMAQUINE P.FALCIPARUM P.VIVAX PRIMAQUINE SINGLE DOSE –DAY 1 AGE (yrs.) mg BASE No. Of Tabs (7.5 mg BASE) Below 1 Nil Nil 1-4 7.5 1 5-8 15 2 9-14 30 4 15 & Above 45 6 PRIMAQUINE DAILY DOSE FOR 14 DAYS AGE (yrs.) mg BASE No. Of Tabs (2.5 mg BASE) Below 1 Nil Nil 1-4 2.5 1 5-8 5 2 9-14 10 4 15 & Above 15 6

ACT (Artesunate + SP) dosage schedule for P. falciparum cases in chloroquine resistant areas:

ACT (Artesunate + SP) dosage schedule for P. falciparum cases in chloroquine resistant areas

Malaria Drug policy 2009:

Malaria Drug policy 2009

Active intervention measures:

Active intervention measures STRATIFICATION OF PROBLEM Provides guidelines which are most suited and economical under existing conditions Endemic areas have been stratified according to API Areas with API <2 Areas with API >2

MOSQUITO CONTROL MEASURES:

MOSQUITO CONTROL MEASURES 1). ANTI-LARVAL MEASURES: (a) Environmental control. (b) Chemical control. (c) Biological control. 2). ANTI ADULT MEASURES: (a) Residual sprays. (b) Space sprays. (c) Genetic control. 3 ).PROTECTION AGAINST MOSQUITO BITES : (a) Mosquito nets. (b) Screening. (c) Repellents.

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ANTI-LARVAL MEASURES : a) ENVIRONMENTAL CONTROL: The most important step in reducing the numbers of mosquitoes is to eliminate their breeding places- "source reduction", and comprises minor engineering methods such as filling, leveling and drainage of breeding places and water management. Source reduction also implies rendering the water unsuitable for mosquito breeding ( changing the salinity of water).

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b) CHEMICAL CONTROL : The commonly used larvicides are : ( i ) Mineral oils (ii) Paris green (iii) Synthetic insecticides ( i ) Mineral oils : The application of oil to the water. The oils most widely used are the diesel oil, fuel oil, kerosene and various fractions of crude oils. Special oils like Mosquito Larvicidal Oil are also available.

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When applied on water, oil spreads and forms a thin film, which cuts off the air supply to the mosquito larvae and pupae. The usual application rate for oils is 40 to 90 litres per hectare. Oil has also certain disadvantages. It renders water unfit for drinking. It kills fish.

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( ii) Paris green : Paris green or copper acetoarsenite is an emerald green, micro-crystalline powder practically insoluble in water. A good sample of Paris green must contain 50 percent arsenious oxide. Paris green is a stomach poison and to be effective it must be ingested by the larvae. Paris green kills mainly the Anopheles larvae because they are surface feeders.

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(iii) Synthetic insecticides : Fenthion, Chlorpyrifos, and Abate are the most effective larvicides . Abate at a concentration of 1.0 ppm has been found to be a very effective larvicide, and also the least toxic. The organochlorine compounds (e.g., DDT, HCH) are not recommended for larviciding operations because of their long residual effect, water contamination and increased risk of developing resistance in the vector mosquitoes.

Insecticides:

Insecticides

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c)Biological control: A wide range of small fish feed readily on mosquito larvae. The best known are the Gambusia affinis and Lebister reticulatus (sometimes known as Barbados Millions). These fish can be used in burrow pits, sewage oxidation ponds, ornamental ponds, cisterns and farm ponds. Biological control can be effective only when used in conjunction with other methods.

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(Guppy) Poecilia reticulata Gambusia affinis

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2. ANTI-ADULT MEASURES: (a) Residual sprays: Adult mosquitoes are controlled by spraying houses with residual insecticides. DDT is the insecticide of choice, dosages of 1-2 grams of pure DDT per sq metre is applied 1-3 times a year to walls and other surfaces where mosquitoes rest. In areas where DDT resistance is encountered, malathion and propoxur(OMS-33), and to a lesser extent gamma-HCH (lindane) are recommended.

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(b) Space sprays Insecticidal formulation is sprayed into the atmosphere in the form of a mist or fog to kill insects. The common space sprays are : ( i ) Pyrethrum Extract- An extract of pyrethrum flowers is an excellent space spray. The active principle (pyrethrin) is a nerve poison and kills insects instantly on mere contact. For domestic purposes, the hand gun with a fine nozzle is necessary, but for application on a large scale power sprayers or "aerosol" dispensers are needed.

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(ii) Residual Insecticides : New equipment has been developed for ULV (ultra low volume) space spraying. The most extensively used insecticides are malathion and fenitrothion for ULV fogging.

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(c) Genetic control : In recent years, control of mosquitoes by genetic methods such as sterile male technique, cytoplasmic incompatibility, chromosomal translocations, sex distortion, and gene replacement have been explored. Their use is still in the "Research Phase". These techniques have great potential in mosquito control. They also have certain advantages over chemical methods, being cheaper and potentially more efficient and above all not subject to vector resistance.

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3. PROTECTION AGAINST MOSOUITO BITES : (a ) Mosquito net : It offers protection against mosquito bites during sleep. The material of the net should be white, to allow easy detection of mosquitoes. The top and the sides of the net should be of netting. The best pattern is the rectangular net. There should not be a single hole or rent in the net. The size should not exceed 0.0475 inch in any diameter. The number of holes in one square inch is usually 150.

Mosquito Protection:

Mosquito Protection

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(b) Screening : Screening of buildings with copper or bronze gauze having 16 meshes to the inch is recommended. The aperture should not be larger than 0.0475 inch. Screening of buildings is costly, but gives excellent results

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(c) Repellents: Diethyltoluamide has been found to be an outstanding all-purpose repellent . There are others also which are effective: indalone, dimethyl phthalate,dimethyl carbate, ethyl hexanediol, etc. Repellents are used mainly for application on the skin, and their chief advantage is the short duration of protection.

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INTEGRATED CONTROL TO REDUCE OVER DEPENDANCE ON RESIDUAL INSECTICIDES INTEGRATE BIOENVIRONMENTAL & PERSONAL PROTECTION MEASURES 95

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Malaria vaccines vaccination against malaria is a burning issue today. Over the past decades, there has been significant progress in malaria vaccine development, yet many valid candidate vaccines have been slow to enter clinical trial and an effective vaccine is thought to be at least 10 years away. Unlike other vaccines, a malaria vaccine even with only 50% efficacy would still be very useful in controlling the disease.

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hard to develop a vaccine that is effective and affords long term protection spf66 was not effective in phase iii trials in kids under 1 yr RTS s/AS02 are currently being tested in gambia protected 70% of the adults in the trails

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ROLL BACK MALARIA IS A GLOBAL PARTNER SHIP FOUNDED IN 1998 BY WHO, UNICEF, UNDP &WORLD BANK. AIM : TO HALF THE WORLDS MALARIA BURDEN BY 2010.

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GOAL FOR 2010 -TO ENSURE THAT BY 2005 ATLEAST 60% OF THOSE SUFFERING FROM MALARIA SHOULD HAVE PROMPT ACCESS TO TREATMENT WITHIN 24 HOURS OF ONSET OF SYMPTOMS. -ATLEAST 60% OF THOSE AT RISK ( PREGNANT WOMEN , CHILDREN UNDER 5) SHOULD HAVE ACCESS TO INSECTEICIDE TREATED BEDNETS

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ATLEAST 60% OF THE PREGNANT WOMEN SHOULD HAVE ACCESS TO CHEMOPROPHYLAXSIS OR PRESUMPTIVE TREATMENT. POLITICAL COMMITMENT IS KEY PRIORITY OF RBM . HIGHLIGHTS : STRENGHTENING OF HEALTH SYSTEM AND CAPACITY BUILDING

Newer species:

Newer species A fifth species, Plasmodium knowlesi , causes malaria in macaques but can also infect humans.

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