Slide 1

Malariaclinical features and management Chair person Dr P.V. VenkataramanappaProfessorDept .of General medicinePresenter Dr Amar PatilPG Gen Medicine

IntroductionEpidiemology Life cycleClinical featuresSevere malariaMalaria in pregnancyRelapse Treatment of uncomplicated and complicated severe malariaChemoprophylaxisprevention

Introduction Malaria continues to pose a major public health threat in india, particularly due to plasmodium falciparum.Malaria occurs mostly in the tropics. India harbours both p.vivax and p.falciparum and contributes to 70% of malarial cases in south-east asian regions.

According to the World Malaria Report 2014,22% (275.5m) of Indias population live in high transmission (> 1 case per 1000 population)areas,67%(838.9m) live in low transmission (01 cases per 1000 population) areas and 11% (137.7m)live in malaria-free (0 cases)areas.In 2013, 0.88 million cases have been recorded, with 128 million tests being conducted on the suspected cases, withP. falciparumcausing 53% andP. vivaxcausing 47% of the infections. The incidence of malaria in India accounted for 58% of cases in the South East Asia Region of WHOWHO. World Malaria Report 2014. WHO, Geneva. 2014

At present, official figures for malaria in India, available at NVBDCP, indicate 0.71.6 million confirmed cases and 400-1,000 deaths annually.The biggest burden of malaria in India is borne by the most backward, poor and remote parts of the country, with >90-95% cases reported from rural areas and 2000mts because development in the mosquito cannot takes place.The optimum conditions for transmission are high humidity and an ambient temperature between 20 and 30c.

The human host

The behaviour of man also plays an important role in the epidemiology of malaria. There must be a human reservoir of viable gametocytes to transmit the infection.In areas where there is long dry season, and malaria is highly seasonal, the reservior for malaria transmission is in people who asymptomatically harbour parasites for long periods until the next rainy season.

Malaria parasite life cycleInfection with human malaria begins when feeding female anopheline mosquito inoculates plasmodial sporozites at the time of feeding. The small motile sporozites are injected during the phase of probing as the mosquito searches for a vascular space before aspirating blood.

After injection, they enter the circulation, either directly or via lymph channels(approx 20%) and rapidly target the hepatic parenchymal cells.Each sporozite bores into the hepatocyte and there begins a phase of asexual reproduction.This stage lasts on average between 5.5(p.falciparum) and 15 days(p.malariae) before the hepatic schizont ruptures to release merozites.

Period of Pre erythrocytic cycleP.vivax 8 daysP.falciparum 6 daysP.malariae - 13 16 days,P.ovale 9 days

In p.vivax and p.ovale infections a proportion of the intrahepatic parasites do not develop, but instead rest inert as sleeping forms or hypnozoites. To awaken weeks or months later and cause relapses which characterize infections with these two species.During the pre-erythrocytic or hepatic phase of development considerable asexual multiplication takes place and many thousands merozoites are released from each ruptured infected hepatocyte.

Erythrocytic Schizogony(asexual blood stage development)The merozoites liberated in the blood stream closely resemble sporozoites. They are motile ovoid forms which invade the red cells rapidly.Once inside the erythrocyte, the parasite lies within the erythrocyte cytosol enveloped by its own plasma membrane. During the early stages of development(30) IPTp(intermittent preventing therapy in pregnant women) with sulphadoxine-pyrimethamine is recommeneded.

Vaccines for MalariaThis degree of protection would be extremely difficult to achieve and might not be technically feasible with current vaccine art and science.Many vaccine developers have therefore focused their efforts on creating a vaccine that limits the ability of the parasite to successfully infect large numbers of red blood cells. This would not prevent infection but would limit the severity of the disease and help prevent malaria deaths.

Current InitiativesThe PATH Malaria Vaccine Initiative and partner, GlaxoSmithKline Biologicals, published recent Phase 2 trial results showing that the vaccine candidate, RTS,S, has a promising safety and tolerability profile and reduces malaria parasite infection and clinical illness due to malaria.This was the first RTS,S vaccine trial in African infants.

Current successful TrailsIn Phase IIa trials, RTS,S/AS02 protected 4086% of malaria-naive individuals after artificial challenge.Phase IIb trials demonstrated a partial delay of infection, a 30% reduction in clinical episodes of malaria, and reduction in severe malaria by 58%.A phase III trial of RTS,S has been conducted in 11 countries of sub-Saharan Africa from March 2009 through January 2011, in 15460 children.The first results have shown a reduction in the total number of episodes of clinical malaria by 55.1% and reduction in severe malaria by 47%, both in the older group.The RTS,S Clinical Trials Partnership. First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children.New Eng J Med. October 18, 2011. doi: 10.1056/NEJMoa1102287

Prevention Malaraia vector control measures

Action For individual and family protectionFor communityprotectionReduction of human mosquito contactInsecticide treated nets, repellents, protective clothingInsecticide treated netsDestruction of adult mosquitoesIndoor residual spraying, space sprayingDestruction of mosquito larvaeDomestic sanitationLarviciding of water surfaces, biological controlSource reductionSmall scale drainageEnvironmental sanitation, drainage management

Anti-adult measuresResidual spraying : the spraying of houses with residual insecticides(eg: DDT, malathion, fenitrothion) is still most effective measure to kill the adult mosquito.Space application : it involves the application of pesticides in the form of fog or mist using special equipment.Individual protection : man vector control can be reduced by other preventive measures such as use of repellents, protective clothing, bed nets.

Anti larval measuresLarvicides : anti larval measures such as oiling the collection of standing water.Source reduction : techniques to reduce mosquito breeding sites which include drainage, flushing, management of water level, intermittent irrigation.

References Parks textbook of preventive medicine. 23rd edition. The malaria .pg 255-70.Harrisons principles of internal medicine.19th editionMansons tropical diseases.22nd edition section 10,malaria.pg 1201-74.National Drug Policy on Malaria 2013. Directorate of National Vector Borne Disease Control Programme. Govt. of India. New Delhi. 2013Meghna Desai, Feiko O ter Kuile, Franois Nosten, Rose McGready, Kwame Asamoa, Bernard Brabin, Robert D Newman. Epidemiology and burden of malaria in pregnancy.Lancet Infect Dis2007;7:93104

Ashwani Kumar, Neena Valecha, Tanu Jain, Aditya P. Dash. Burden of Malaria in India: Retrospective and Prospective View.Am J Trop Med Hyg.2007;77(6_Suppl):69-78.WHO. World Malaria Report 2014. WHO, Geneva. 2014

Thank you

The recommendations for short term prophylaxis(less than 6weeks) are as follows:1 antimalarials that have to be taken daily should be started one day before arrival in the risk area.2 weekly chloroquine should be started 1 week before arrival.3 weekly mefloquine should be preferbly started 2-3 weeks before departure4 All prophylactic drugs should be taken with unfailing regularity for the duration of the stay in the malaria risk area, and should be continued for 4 weeks after the last possible exposure to infection.

The recommendations for long term prophylaxis(more than 6 weeks) are as follows1 The person who has taken 300mg of chloroquine weekly for over five years and requires further prophylaxis should be screened twice yearly for early retinal changes.Mefloquine is contraindicated in cases with history of convulsions, neuropsychiatric problems and cardiac problems.Available data on long term chemoprophylaxis with doxycycline is limited.