Epidemiology of Malaria, clinical features, treatment

and its control

Dr.J.Nuchin. M.D.,M.B.A.,D.C.A.

Epidemiologist 16-03-2011

By the end of session, you would be expected to be able to describe:

Problem statement Life cycle of parasiteType of vectorClinical features8 important CFs of severe complicated malariaTreatment Diagnosis Control measures

Sir Ronald Ross (1857-1932)

• 1897: role of the mosquito.

• Nobel prize: 1902

Introduction… A protozoan disease caused by a parasite plasmodium A major parasitic cause of death in man One of the oldest recorded diseases Egyptian mummies with enlarged spleens (1000 BC). Hippocrates (460-370 B.C.)-Clear discussion of quartan and

tertian fevers made by in his Book of Epidemics, Noted relationship between enlarged spleens and marshes.

Region between Tigris and Euphrates was malarious (2000 BC).

Malaria was well known to the Ancient Greeks and Romans. The Romans thought the disease was caused by bad air (mal-

aria) from swamps, which they drained to prevent the disease. A tropical disease-considered as ‘king of tropical diseases’

Problem statement-World Has been a scourge of

mankind for the centuries Total death toll due to

malaria is more than that due to any other diseases or even wars

Endemic in 109 (in 2006) countries covering about 45% of global population

Burden – 300-500 million cases and 2-3 million deaths

African countries contribute 90% of the total burden

• Kills a child every 15 to 20 seconds or 8000 children per day

• Nine of 10 deaths globally are among sub-Saharan children under age 5.

• Responsible for 25% total child mortality in Africa

• 90 percent of global incidence of malaria occurs in 13 countries of Africa.

• Out of this more than 50% of cases are from Nigeria, Congo, Ethiopia, Tanzania and Kenya.

• In pregnant women, it causes abortion, still births, LBWs and neonatal deaths globally.

Indian scenario Has always been a home ground for malaria Before 1947 (preDDT era)- malaria was a major cause of

death In 1908, an outbreak in UP and Punjab killed more than

3 lakh people in just a span of 2 months In 1947, India had about 75 million cases and >50% of

total deaths were due to Malaria alone • All the aspects of life were affected directly or indirectly• Industrial and agricultural production was very low• At present, 2-2.5 million cases are being reported with

1000 deaths every year

1947

1961

1965

1976

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

2002

2003

2004

2005

0

10

20

30

40

50

60

70

80

75

6.47

1.81

No. of malaria cases( In Millions) in India since 1947 to 2005

In 1950s, India used to report about 75 million every year with around 7.5 million deaths

1961

1965

1976

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

2002

2003

2004

2005

0

1

2

3

4

5

6

7

Pv and Pf cases in millions since 1947 to 2005 in India

Major malaria ecotypes found in India

• Rural malaria-• Urban malaria-• Forest malaria• Irrigation malaria• Project malaria• Migration malaria• Border malaria

Factors responsible for the increase in VBDs

Poverty and rapid population growth IrrigationUrbanization and improper sanitation IndustrializationMigration and rapid population movementNatural disastersResistanceGlobal warmingPolitical instability Inadequate health infrastructure

1.1 billion people live on less than $1 a day.

2.7 billion people live on less than $2 a day.

IRRIGATION IN INDIA

22.626.25 29.12 30.57

37.141.21

52.0256.81

91.02

78.12

0

20

40

60

80

100

Pre 1st 1951-56

IInd1956-61

IIIrd1961-66

Annual1966-69

IVth 1969-74

Vth 1974-78

Annual1978-80

VIth1985-90

VIIth1990-95

Mill

ion

Hec

tare

s

Karnataka

A major CMD in the state. 7 districts namely DK,G,R,K,T,Bijapur and Bagalkot

together contributed >65% of the total burden in the state in 2010

The P.f cases are being decreased in Karnataka and not so in other parts of the country.

Double resistance has been recorded

MALARIA CASES IN Karnataka since 2006 to 2010

2006 2007 2008 2009 2010

62842

4935547344

36859

44108

Karnataka in 2006- 62864 cases

Dakshina kannada

21%

Kolar13%

Raichur12%Gulbarga

8%

Tumkur7%

Belgaum7%

Others32%

85% of the cases in the state were due to these 11 districts with 2 deaths in the year 2008

Kolar, 11%

Tumkur, 2%

Chitradurga, 4%

Bijapura, 6%

Bagalkot, 4%

U. Kannada, 1%

Gulbarga, 16%

Bellary, 4%

Raichur, 14%

Koppal, 9%

D.Kannada, 15%

% OF MALARIA CASES IN THE STATE-2008

85% of the case s in the s tate wer e

due to these 11 d istricts w ith 2 deaths

Contribution of malaria cases in the year 2009 in 10 districts of Karnataka- Total no of cases-36859.

Gulbarga

D.Kannada

Raichur

Koppal

Tumkur

Bijapura

Bagalkot

Chikkaballapura

Bellary

Udupi

28%18%

13%

8%

7%

6%

5%

5%

4%

4%

85% of the total cases in the year contributed by these 10 districts

No. of cases in 2010-Karnataka->85% of cases were due to these10 districts

Chitradurga

Udupi

Tumkur

Bijapura

Raichur

Bagalkot

Bellary

Koppal

D.Kannada

Gulbarga

1062

1483

1953

2047

3166

3702

3942

4105

6280

7100

2010

2006

2007

2008

2009

2010

24.5%

37%

23.2%

17.8%

18.2% PFR in Karnataka From 2006 to 2010

• Malaria status in Belgaum

Geographically the district has been divided into 3 parts

1) Hilly region- Khanapur 2) (South) Semi Malnad

– Savdatti, Hukkeri, Bailhongal and Belgaum

3) (North) Tropical Region- Athani, Raibagh, Gokak, Ramdurga and Chikkodi Taluks

Belgaum district• Taluks-10• GHs-9• CHCs-16• PHCs-140• SCs-660• M.O.s-165, HWs-745,LTs-121• Villages-1160• Rural population-3201814 (2001 census)• Urban population-1012691• Total population-4214505• Density-314 per sq mtr

• The average rain fall in the district is 808mm every year.

• Krishna, Malaprabha and Ghata prabha being the major rivers in the districts, it also has five small rivers namely Markhandeya, Hiranyakeshi, Mahadaayi, Vedaganga and Dudhaganga. Navilu Tirtha dam is built for Malaprabha river in Savadatti taluka and Hidkal dam for Ghataprabha river in Hukkeri taluka. These two huge dams provide irrigation facilities through canals for the 8 taluks of the district

• With many historical places to its credit and plenty of Jatraas, the district attracts travelers from the near by districts and neighboring states all through the year

Talukwise Malaria incidence-2008

Gokak59%

Savdatti18%

Ramdurg13%

Bailhonngal4% Belgaum

4%

Talukwise malaria incidence-2007

Gokak68%

Ramdurg13%

Soundatti10%

Bailhongal5%

Gokak23%

Bhailhongal10%

Belgaum11%

Khanapur5%

Ramadurga32%

Soudatti18%

Talukawise incidence of malaria cases-2009 Total cases-456

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

1251

2066

1576

879

633

1490

574

400

692

601

2102

63344343

2689

989

352869

1674

2859

4149

3908

2226

456

537

Malaria burden in Belgaum Dist. Since 1987 to 2010

2004

2005

2006

2007

2008

2009

2010

45.20%

39.50%

30.10%

28.00%

21.00%

19.00%

14.89%

PFR in Belgaum districtFrom 2004 to 2010

160

93 80

246

678

589551

386363

237

392 374

1

Mal

aria

cas

es

Jan to Dec

Malaria cases-2006 month wise-Total Cases-4149

Note the 2nd peak of disease

210154

181

299

421

560

429

305279

250

401 419

Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec

Monthwise no. of Malaria cases -2007Note the 2nd peak of disease

643408 373

776

14981849

1483

1072 960 836

1358 1334

0

500

1000

1500

2000

January to December

Monthwise no. of cases-2004 to 2007Note the 2nd peak of disease

Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec

208183 175

242

332355

208

127139

124

7657

Monthwise Malaria cases-2008

208183 175

242

332355

208

127 139 12476 57

Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec

Monthwise Malaria Cases-2008

210154 181

299

421

560

429

305 279 250

401 419

Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec

Monthwise Malaria Cases-2007

Jan Feb Mar Apr May Jun July Aug Sept Oct Nov Dec

29 2415

23 26

101

132

58 57

27 23 22

Month wise Malaria incidence in the district in the year 2010-Total no. of cases- 537

Jan Feb Mar Apr May Jun July Aug Sept Oct Nov Dec

4035 37

3329

3945

42

3036

41

49

Month wise incidence of Malaria in the year 2009- Total no. of cases-456

What’s the Good News?

• Every one of these deaths is preventable!!!

• Just a 3 day course of treatment can cure the disease

• No stigma associated with malaria• No “Save the Mosquito” groups

Endemicity and immunity to malaria

Endemicity Malaria is said to be endemic when there is a constant incidence

of cases over a period of many successive years. Endemic malaria may be present in various degrees. There are four grades A. Hypoendemicity – There is a little transmission and the disease

has little effect on the population. B. Mesoendemicity - varying intensity of transmission; typically

found in the small, rural communities of the sub-tropics. C. Hyperendemicity - intense but seasonal transmission; immunity

is insufficient to prevent the effects of malaria on all age groups.

contnd…

D. Holoendemicity - intense transmission occurs throughout the year. - As people are continuously exposed to malaria parasites, they gradually develop immunity to the disease.

- In these areas, severe malaria is mainly a disease of children from the first few months of life to age 5 years.

- Pregnant women are also highly susceptible Although seasonal variations in transmission may occur in holoendemic

areas, malaria transmission occurs all year round. Therefore, people acquire natural immunity and epidemics are unlikely.

Contnd…

Depending on the intensity of transmission, malaria can be stable or unstable, reflecting different epidemic scenarios.

Stable malaria: Sustained incidence over several years. Seasonal fluctuations in transmission may occur but epidemics are unlikely.

Unstable malaria: Marked variations in the incidence of malaria over

time. Population does not develop immunity and people of all ages are susceptible to severe disease when transmission increases.

Agent –Parasite-Plasmodium• Unicellular • 140 types are there of which only 4 can infect

man(P.vivax, falciparum, ovale and malariae)• Malaria also affects other animals like primates,

rodents, birds, bats and even cold blooded animals like lizards

• Some parasites infecting primates can also infect man- eg,-P.knowelesi, P.brasilianum and P.cyanomalgi

• Monkey malaria

Figure 11.30

Plasmodium Sporozoite

Different speciesP.vivax- all over world-less common in Africa

60-70% BTM MildAnaemia, splenic rupture rarely

P.falciparum-tropics and sub-tropics

25-35% MTM High degree parasitaemia, all deaths

P.malariae <1% BQM NS, found in Karnataka

P.ovale-very rare

NF BTM OM, in Africa

Mode of transmission

1. By bite of female anopheles mosquitoes2. By blood- Blood transfusion and contaminated

syringes and needles3. Mother to foetus.

Congenital malaria• Occurs in 5% of the babies borne to mothers who were

MP positive during pregnancy• Transplacental infection

– Can occur in all 4 species– Commonly seen P.v. and P.f. in endemic areas– P.m. infections in nonendemic areas due to long persistence of

species• Neonate can be diagnosed with parasitemia within 7 days

of birth • Fever, irritability, feeding problems, anemia,

hepatosplenomegaly, and jaundice

Life cycle of plasmodia• The parasite 2 cycles of development- the Human

cycle (asexual cycle) and Mosquito cycle (sexual cycle)

• Man is the intermediate host harbouring the larval stages

• Mosquito is the definitive host harbouring the adult stages

Asexual cycle or Human cycle• Begins with the injection of

sporozoites following the bite of infected mosquito

• Three phases are observed Phase 1-Hepatic phase (pre or

exo erythrocytic or tissue)- Sporozoites disappear from

the circulation within 45-60 mins

Many of them are destroyed by phagocytes and some reach the liver cells

After 1-2 weeks of development (depending upon the species) they become hepatic schizonts

Hepatic Cells with plasmodia

Hepatic schizoint- The actively dividing, multinucleated, parasite form in hepatocytes; produces no inflammatory response.

Pre-erythrocytic schizoints

Contnd… These hepatic schizoints eventually rupture,

releasing showers of merozoites which attack

RBCs.

Erythrocytic schizont: It is a multinucleated stage

in a RBC resulting from asexual multiplication of

trophozoite. Each schizont contains a species

determined number of meroziotes.

Merozoite: is a protozoan cell that arises from the

schizogony of a parent sporozoan and may enter

either the asexual or sexual phase of the life cycle.

Infective to other fresh RBCs.

The number of meroziotes released vary according to

the type of parasite

In case of P.f, as many as 40,000 and in others 2000-15,000 merozoites are released

Trophozoite: Metabolically active form of the malaria parasite living within the RBC; sometimes called the ring form.

In case of P.f, the intrahepatic schizoints rupture almost simultaneously and there is no persistent tissue- no secondary exo erythrocytic stage

On the contrary, the intrahepatic schizonts of other plasmodia do not burst all at the same time.

Some intrahepatic schizonts persist and remain dormant (hypnozoites) for considerable periods and later they cause relapses

Once the parasites enter RBCs, they do not reinvade the hepatic cells

Phase 2- Erythrocytic phase (erythrocytic schizogony)

Many of the merozoites are quickly destroyed and significant number of merozoites bind and enter the RBCs

Then they pass through the stages of trophozoites and schizonts

Each parasite spends two days in a red blood cell consuming the hemoglobin and reproducing.

Malaria parasites invading an RBC

Malaria parasites in the RBCs

Erythrocytic Schizogony• nuclear division =

begin schizont stage• 6-40 nuclei• budding merozoites =

segmenter• erythrocyte rupture

releases merozoites

gametocytes

erythrocytic schizogony• 48 hr in Pf, Pv, Po• 72 hr in Pm

Erythrocytic forms (signet)

Young ring form trophozoites

RBCs rupture releasing merozoites which infect the fresh RBCs

16 new parasites burst out to infect other red blood cells from each merozoite

The sporozoites first invade liver cells and asexually reproduce to produce huge numbers of merozoites which spread to red blood cells where more merozoites are produced through more asexual reproduction.

Duration of erythrocytic phase is constant for species to species

It is 48 hrs in case of P.v, P.f and P.o whereas 72 hrs in P.m

The cycle may be repeated many times and may end with complications or be slowed down by immunity of the host

Phase 3- Gametogony Some of the erythrocytic

forms do not divide but become male (smaller) and female (longer) gametocytes

These are infective to mosquitoes

Gametocytes always circulate in the subcutaneous capillaries

Characteristics of different speciesSpecies Duration of

tissue phase (days)

Incubation period (days)

Number of merozoites

/ cell

Red cells invaded

P. falciparum

5.5 – 7 8 - 11 40,000 cells of all ages

P. vivax 6-8 10 - 17 10,000 reticulocytes

P. ovale 9 10 – 17 15,000 reticulocytes

P. malariae 12-16 18 - 40 2,000 mature cells

Sexual or mosquito cycle

These infective gametocytes are ingested by the anopheles mosquitoes

Then develop and undergo stages of fertilisation- zygote, ookinate, oocyst and sporozoites

Sporozoites enter the salivary gland from the gut and are infective to man

Once in the mosquito, Plasmodium needs about 8-10 days to produce sporozoites that are ready to be injected into a human.

Plasmodia in Anopheles

Vector-Anopheles• Anopheles mosquitoes

65

Egg

6 – 8Days

Complete MetamorphosisTotal = 10 – 12

days

2 Days

2 Days

Life Cycle- 7days at 310c,20 days at 200c

Sl.No.

Common geographical area

Malaria vector Features

1 Urban area A.stephensi Breeds in used wells, overhead tanks2 Rural area A.culicifacies Zoophilic, wide distribution, high density required

for transmission, breeds in stagnant water, found in plains

3 Hilly area A.fluvitalis More anthrophilic, less density required for transmission, breeds in slow running water

4 Coastal area A.sundaicus Breeds in salt water,exophilic

5 Plantation area/Malnad area

A.minimus Breeds in slow running water

6 In water logging area

A.Philippensis Breeds in high level subsoil water, found in plains

Disease Potential is high in An. Minimus, An. Dirus, An. Fluviatilis, medium in An. stephensi An. sundaicus and low in An. culicifacies

An.culicifacies Breeding Sites

Host factors

Malaria affects all ages, but rare in newborn due to presence of foetal haemoglobin and maternal immunity

Common in males because of outdoor activities and clothing pattern (816 F -45% and 1014 M-55% out of 1830 in Belgaum till JAN 1998 to August 2008)

Duffy negative people are resistant to P.v. Most of the Africans are Duffy negative, this explains why P.v is not so common in Africa

Patients of SC trait ( Hb AS), G6PD and thalasseamia are less likely to be affected by malaria

High risk group Pregnant mothers- have an increased risk of severe malaria especially

in primigravidae, as the immunity to the malaria is impaired in pregnancy.Pregnant women attract twice the number of mosquitoes than non-pregnant women There is a greater susceptibility to P. falciparum than P. vivax during pregnancy

Children - Malaria affects cognitive development and learning abilities of children.

• Malaria is a risk factor of neuro-sensory and behavioral development in children

Immigrants from Europe- as they lack natural immunity

Immunity

• Occurs only after repeated exposure to the disease• Influenced by

– Genetics– Age– Health condition– Pregnancy status– Intensity of transmission in region– Length of exposure– Maintenance of exposure

Incubation period It is the length of time between the bite of infected

mosquito and appearance of first clinical feature (ie,fever). It is about 10-12 days in P.f and 10-14 days in other species

Prepatent period This is the length of time between the bite of infected

mosquito and appearance of parasites in peripheral blood

Clinical course

• Following a bite by an infected mosquito, many people do not develop any signs of infection. If infection does progress, the outcome is one of three depending on the host and parasite factors enumerated in the previous slides:

– Asymptomatic parasitaemia (“clinical immunity”)– Acute,(Simple) uncomplicated malaria– Severe malaria

Asymptomatic parasitaemia

• This is usually seen in older children and adults who have acquired natural immunity to clinical disease as a consequence of living in areas with high malaria endemicity.

• There are malaria parasites in the peripheral blood but no symptoms.

• These individuals may be important reservoirs for disease transmission.

• Some individuals may even develop anti-parasite immunity so that they do not develop parasitaemia following infection.

Simple, uncomplicated malaria

• This can occur at any age but it is more likely to be seen in individuals with some degree of immunity to malaria. The affected person, though ill, does not manifest life-threatening disease.

• Fever is the most constant symptom of malaria. It may occur in paroxysms when lysis of red cells releases merozoites resulting in fever, chills and rigors (uncontrollable shivering).

The periodicity of malaria fever• The first febrile attack corresponds to the development of parasites in the RBCs.• The fever may be continuous or remittent before it

becomes classically intermittent• Intermittent nature of the fever is due to cyclical release of

merozoites following rupture of infected RBCs• It is once in 48 hours in case of P.v, P.f (36 hrs- sub-tertian)

and P.o whereas 72 hours in P.m (erythrocytic schizogony is the time taken for

trophozoites to mature into merozoites before release when the cell ruptures).

Contnd…• A typical attack involves 3 distinct stages (in a

person from non-endemic area). Cold stageBegins with feeling of cold, shivering and headachePatient covers himself with blankets, BT reaches 39-

410CIt may continue for 15 mins to 1 hour

Parasites are demonstrable in the blood

Contnd…

Hot stage The fever raises so high so the patient feels

burning hot and takes off the clothesThe patient feels intense headache with nausea and

vomitingPulse is of bounding type, patient feels thirsty and it

may continue for 2-6hrs

Sweat stage Fever comes down with profuse sweatingHe goes usually into deep sleepLasts for 2-4 hoursFebrile herpes is very common Malaria- one clinical febrile episode of malaria

consumes 5,000 k Cal.

Note how the frequency of spikes of fever differ according to the Plasmodium species. In practice, spikes of fever in P. falciparum, occur irregularly - probably because of the presence of parasites at various stages of development.

Other features of simple, uncomplicated malaria include:

Malaria is a multisystem disease. Other common clinical features are: Vomiting

Diarrhoea – more commonly seen in young children and, when vomiting also occurs, may be misdiagnosed as viral gastroenteritis

Convulsions – commonly seen in young children. In an endemic area, cerebral malaria should be ruled out if any child fails to regain consciousness within an hour after an episode of febrile convulsion.

Pallor – resulting mainly from the lysis of RBCs. Malaria also reduces the synthesis of red blood cells in the bone marrow.

Jaundice – mainly due to haemolysis. (Serum bilirubin > 50 mol/1 or > 3 mg/dl.).

Contnd…

Anorexia Cough Headache Malaise Muscle aches Splenomegaly Tender hepatomegaly

These clinical features occur in “mild” malaria. However, the infection requires urgent diagnosis and management to prevent progression to severe disease.

Hepatosplenomegaly

Severe and complicated malaria

Although severe malaria is both preventable and treatable, it is frequently a fatal disease.

0.5 -2% of the total P.f malaria develop complications and of which 50% are fatal

The following are 8 important severe manifestations of malaria

1. Severe malaria anaemia2. Cerebral malaria3. Hypoglycaemia4. Metabolic acidosis5. Acute renal failure6. Pulmonary oedema7. Circulatory collapse, shock or “algid malaria”8. Blackwater fever

Note: It is common for an individual patient to have more than one severe manifestation of malaria!

Anaemia in malaria-Severe anaemia(haematocirt < 15% or haemoglobin < 5 g/dl).

It is severe in P.f infections as it attacks 20-35% of total RBCs whereas only 1% is affected in other plasmodia

CausesHaemolysis of infected RBCsHaemolysis of uninfected RBCsDyserythropoiesis (Bone marrow)Splenomegaly-erythrocyte sequestrationDepletion of folate stores

Immediate blood transfusion is required in majority of patients

Cerebral malaria• The most well-known severe manifestation of

malaria. Responsible for 80% of the total malaria deaths.

• Defined as:– unarousable coma persisting for more than

one hour – with asexual forms of P. falciparum in the

peripheral blood– other common causes of encephalopathy

excluded (WHO1999)Common in P.f infections where the erythrocytic schizogony takes place in the smaller capillaries of the internal organsResults in the blockage of capillaries by parasitized RBCs.

• reduced cerebral blood flow• cerebral hypoxia• release of cytokines

A 4 year old boy who was deeply comatose and had persistent deviation of the eyes

A young girl with cerebral malaria. Note the abnormal, decerebrate posturing

Occurs most commonly in young children although non-immune adults are also at risk.Cerebral malaria can rapidly progress to death, even with appropriate treatment. Case fatality is between 20-50%.

The illness may start with drowsiness and confusion and then progress to coma. The loss of consciousness is often preceded by repeated convulsions. Retinal haemorrhages may be seen on fundoscopy. In survivors, resolution of coma usually occurs within 1-2 days in children and within 2-4 days in adults but may be complicated by neurological sequelae in ~5% adults and >10% of children.

3. Hypoglycaemia

Blood sugar <2.5 mmol/L (i.e.,<40 mg/dl).

• Increases the risk of mortality and sequelae in children with cerebral malaria; may present with convulsions or a deterioration in level of consciousness.

• Results from a combination of factors:– reduced glycogen stores because of reduced food intake– increased metabolism due to fever and repeated

convulsions– glucose consumption by malaria parasites– cytokine or quinine-stimulated hyperinsulinaemia

4. Metabolic acidosis• Lactic acidosis is a major contributor and probably results from

tissue anoxia and anaerobic glycolysisPresents with deep, rapid respirations (as in diabetic ketoacidosis) Acidaemia (arterial pH < 7.25) or Acidosis (plasma bicarbonate < 15 mmol/1).

Lactic acidosis results from : Anaerobic glycolysis due to microvascular obstruction. Failure of hepatic and renal lactate clearance. Production of lactate by the parasite. Lactate levels rise after generalized convulsions.

5. Acute renal failure

• Occurs almost exclusively in adults and older children in areas of unstable malaria

• The kidneys are often slightly swollen. Tubular abnormalities consistent with acute tubular necrosis (ATN) are seen.

• Sequestration in glomerular capillaries,mesangial endothelial cell proliferation, and immunoglobulin deposits may be seen.

• Cortical necrosis never occurs.

• Affected patients are usually oliguric (urinary output <400 ml/day) or anuric (<50 ml/day)

• Renal failure may be associated with haemoglobinuria (Black water fever).

• Serum creatinine levels are elevated >3 mg/dl

Nephrosis

P. Malariae quarten nephrosis

Hyperparasitaemia>5% of RBCs are affected-P.falciparum

6. Acute pulmonary oedema

This is a grave and usually fatal manifestation of severe falciparum malaria and occurs mainly in adults.

Hyperparasitaemia (>5% of RBCs are parasitized), renal failure and pregnancy are recognised predisposing factors and the condition is commonly associated with hypoglycaemia and metabolic acidosis.

7. Circulatory collapse, shock, “algid malaria” Systolic BP < 50 mmHg in children and < 80 mmHg in adults defines hypotension/shock. Patient with severe malaria can develop sudden hypotension & become shocked. This is “Algid Malaria”. Features of circulatory collapse- cold/clammy skin, weak/ thready pulses, hypotension, peripheral cyanosis, peripheral vasoconstriction, and rapid feeble pulse with core/skin temperature difference of ≥ 10° C. “Algid malaria” is characterised by hypotension, vomiting, diarrhoea, rapid respiration and oliguria. This condition is associated with a poor prognosis.

8. Haemoglobinuria or “Blackwater Fever”Characterized by rapid, severe, massive intravascular haemolysis.It is associated with infection by P.f, most commonly seen in a non-immune person who has resided in the endemic country for the last 6 months to 1 year and inadequately treated by quinine.In these cases, quinine is a precipitating factor. It is triggered by exposure to cold, sun, fatigue, trauma, pregnancy, X-rays etc,. The condition presents with severe pallor, jaundice and passage of dark urine due to haemoglobinuria. It may be associated with acute renal failure.

A 3 year old boy with severe anaemia (Hb% 3.3 g/dl) and

dark urine (shown in the container)

Typical dark urine of Haemoglobinuria on Day 0 and cleared by Day3

in the clinical features of severe Summary of differences malaria in adults and children

Clinical Manifestation Children AdultsSimilar in adults and children • Prostration • Circulatory collapse

++++

++++

More common in children • Cerebral malaria• Severe anaemia• Multiple convulsions • Metabolic acidosis• Hypoglycaemia

+++ +++ ++++++++

++ +++

+ / -

More common in adults • Jaundice • Pulmonary oedema• Haemoglobinuria • Abnormal bleeding• Renal failure

+ + / - + / - + / -+ / -

++++++++

Frequency of occurrence

DiagnosisMalaria is a multisystem disease. It presents with a wide variety of non-specific

clinical features. None of the clinical features are pathognomonic.Many patients have fever, general aches and pains

and malaise and are initially misdiagnosed as having “flu”.

P. falciparum malaria can be rapidly progressive and fatal.

Diagnosis• A good history

– Residence or a recent visit (in the preceding 3 months) to a malaria endemic area

– History of fever – Recognise significance of non-specific clinical features such as

vomiting, diarrhoea, headache, malaise• Physical examination

– Identify signs consistent with malaria: fever, pallor, jaundice, Splenomegaly

– Exclude other possible causes of fever (e.g. signs of viral and bacterial infections)

The diagnosis of malaria should be considered in any unwell person who has been in a malarious area recently

Blood Film ExaminationThick and thin blood films (or “smears”) have remained the

gold standard for the diagnosis of malaria. The films are stained and examined by microscopy.

Thick blood film - Used for detecting malaria: a larger volume of blood is examined allowing detection of even low levels of parasitaemia. Also used for determining parasite density and monitoring the response to treatment.

Thin blood film – Gives more information about the parasite morphology and, therefore, is used to identify the particular infecting species of Plasmodium.

Appearance of P. falciparum in thin blood films. Ring forms or trophozoites; many red cells infected – some with more than one

parasite

Other methods of diagnosis of malaria

These are not routinely used in clinical practice. a) Antigen capture kits. Uses a dipstick and a finger prick blood

sample. Rapid test - results are available in 10-15 minutes. Expensive and sensitivity drops with decreasing parasitaemia.

b) PCR based techniques. Detects DNA or mRNA sequences specific to Plasmodium. Sensitivity and specificity high but test is expensive, takes several hours and requires technical expertise.

c) Fluorescent techniques- Relatively low specificity and sensitivity. Cannot identify the parasite species. Expensive and requires skilled personnel.

d) Serologic tests- Based on immunofluorescence detection of antibodies against Plasmodium species. Useful for epidemiologic and not diagnostic purposes.

Treatment

The treatment of malaria depends on a number of factors

1. Severity of the infection: whether simple, uncomplicated or severe, complicated malaria.

2. Parasite factors: species, drug sensitivity

3. Patient factors: age, pregnancy, prior chemoprophylaxis, known allergies, likelihood of drug compliance.

Drugs under NVBDCP- Malaria drug policy 20101. Chloroquine 2. Primaquine 3. ACT- Artesunte +Sulphadoxine /Sulfalene + Pyrimethamine

4. Quinine 5. Doxycycline6. Artesunate7. Artemether 8. Arteether

Treatment of uncomplicated malaria

Presumptive treatment: It is given to 1. All fever cases with H/O fever during past 15 days2. All fever cases irrespective of age and sex 3. No Primaquine to infants and pregnant women. 4. Each Chloroquine tab available as 150 mg and

Primaquine tab as 2.5 mg & 7.5 mg.Radical Treatment:5. Given after microscopic confirmation6. No Primaquine to infants and pregnant women. 7. Each Chloroquine tab available as 150 mg and

Primaquine tab as 2.5 mg & 7.5 mg.

PRESUMPTIVE YREATMENT – All fever cases are given tabs even before microscopic confirmation.(No more recommended under

MDP-2010-NVBDCP)No Primaquine to infants and pregnant women. Each Chloroquine tab

available as 150 mg and Primaquine tab as 2.5 mg

Age (Yr)

L R A H R AChloroquine(mg)

Chloroquine(mg) Primaquine(mg)

Base in mg.

Day 1

Day 2 Day 3 Day 1

0-1 75 75 75 37.5 -1-4 150 150 150 75 7.54-8 300 300 300 150 158-14 450 450 450 225 30>14 600 600 600 300 45

RADICAL TREATMENT- After microscopic confirmation No Primaquine to infants and pregnant women. Each Chloroquine tab available as 150 mg and Primaquine tab as 2.5 mg

Age (Yr) P.vivax P.falciparumChloroquine(mg)

Primaquine(mg)14 days

Chloroquine(mg)

Day1 Day2 Day3

Primaquine(mg)

0-1 75 - 75 75 37.5 -1-4 150 2.5 150 150 75 7.54-8 300 5 300 300 150 158-14 450 10 450 450 225 30>14 600 15 600 600 300 45

Site of Action

ChloroquineQuinine, SPArtemisinin

Quinine & Chloroquine in P.V. and Primaquine in P.F.

Primaquine

109

Drug Class

Drugs

Blood Schizontoc

idal

Chloroquine, Quinine, Quinidine, Mefloquine, Halofantrine, Sulfonamides, Tetracyclines,

Atovaquone, Artemisinin compounds Tissue

Schizontocidal

Primaquine, Proguanil, Pyrimethamine,

Gametocidal

Primaquine

Hypnozoitocidal

Primaquine

NA-not active, A-active,

Drug Sporozoites

Primary tissue phase

Asexualparasite

Gametocyte

Hypnozoite

Quinine NA NA A A-P.v NA

Chloroquine NA NA A A-P.v NA

Primaquine A A A in toxic dose

A A

SP Less A Little A on P.f

Incomplete NA NA

Mefloquine NA NA A NA NA

- 236 PHCs in 19 states are identified as Chloroquine resistant.

Avoid these combinations• Most antimalarial drugs have a long plasma half-life. Therefore,

adding similar drugs half way through the treatment will only add to the adverse effects and not to the therapeutic benefit. The following combinations should therefore be avoided, concurrently or within a short interval:

Both sulpha and primaquine can precipitate hemolytic crisis in patients with Glucose 6-phosphate dehydrogenase deficiency.

(1) Chloroquine + Quinine

(2) Chloroquine + Mefloquine

(3) Quinine + Mefloquine

(4) Quinine + Primaquine

(5) Quinine + Halofantrine

(6) Mefloquine + Primaquine

• National drug Policy on Malaria-2010-NVBDCP

National drug Policy on Malaria-2010-NVBDCP

1) Treatment of P.v infections- As discussed earlier2) Treatment of uncomplicated P.f. cases. a) Artemesinin based Combination Therapy-ACT Artesunate 4mg/kgBW daily for 3 days + sulfadoxine(25mg/kgBW)-Pyrimethamine

(1.25mg/kgBW) on 1st dayACT not to be given in 1st trimester of pregnancy(Each Sulfadoxine-Pyrimethamine(SP) contains 500mg

of Sulfadoxine and 25mg of Pyrimethamine)

Age-wise dosage for treatment of P.f cases

3) Treatment of uncomplicated P.f cases in pregnancy:1st trimester-Quinine salt 10mg/kgBW to be given 3 times daily for 7 daysII and III trimester: ACT as per dosage above

4)Treatment of mixed infections: All mixed infections should be treated with full course of ACT and Primaquine 0.25mg/kgBW daily for 14 days

5) Treatment of severe malaria cases: a) Artesunate: 2.4mg/kgBW IV or IM given on

admission, then at 12 hour and 24 hour and then once daily. OR

b) Artemether: 3.2mg/kgBW IM given on admission and then 1.6mg/kgBW per day. OR

c) Arteether: 150mg/kgBw IM daily for 3 daysin adults only (not to be given in children) OR

d) Quinine: 20mg/kgBW on admission (IV infusion or divided IM injection) followed by 10mg/kgBW 8th hrly. Infusion rate should not exceed 5mg/kgBW per hr.

Mass drug administration

• Recommended in API>5 per 1000 popn (WHO)• Not for under 5 children

Chemoprophylaxis- Use of anti-malarial drugs to prevent the

development of malaria is known as chemoprophylaxis.

- Unreliable with development of drug resistance- Started 1 week before arrival in the malarious area and

continued for atleast 4 weeks, preferably 6 weeks after leaving a HRA.

- Should be complemented by personal protection and other VCMs

Chemoprophylaxis - Recommended for 1.Travellers from non endemic areas2.As a short measure for soldiers, police and

labours serving in highly endemic areas3.All ANCs in HRAs- initiated in II semester

MALARIA TREATMENT COST OF

AN ADULT IN INDIADrugs Cost (Rs.) Chloroquine 3.50-10.00Chloroquine injection + fluids 200.00Sulfadoxine Pyrimethamine 7.00-30.00Mefloquine 240.00-300.00Artemether injections 390.00-1000.00Arteether injections 275.00Artesunate injections 1120.00Quinine tables + Tetracycline 270.00-210.00Quinine injections+IV fluid+Tetracycline 800-910 *Antipyretics @ Rs. 5.00-10.00 per treatmentI/V fluid may be required during Artemisinin treatment

HIV,Pregnant women and their fetus/newborn

• HIV does make malaria in pregnancy worse– More and higher density malaria, more illness, more

anemia, more low birth weight

• Malaria may make HIV worse– Higher HIV viral load – ? impact on Mother-to-Child Transmission (MTCT)

The Worlds Priorities? Annual ExpenditureGlobal Reduction in Malaria $ 1 billionBasic education for all $ 6 billion Cosmetics in the US $ 8 billionSafe water and sanitation $ 9 billion Ice cream in Europe $ 11 billionReproductive health for all women $ 12 billion Perfumes in Europe and the US $ 12 billion Basic health and nutrition $ 13 billion Pet food in Europe and the US $ 17 billionBusiness entertainment in Japan $ 35 billionCigarettes in Europe $ 50 billionAlcoholic drinks in Europe $ 105 billionNarcotic drugs in the world $ 400 billionMilitary spending in the world $ 780 billion

Source-Favaloro et al Circulation 1999

Prevention and Control of Malaria

Malaria vaccine

A burning issueSeveral vaccine candidates are now being tested in Africa, Asia and USA.Vaccines such as SPf66, RTs, S/AS02 developed by some countries failed to show required efficacy.Unlike other vaccines, a malaria vaccine even with only 50% efficacy would still be a very useful in controlling the disease.An effective vaccine is thought to be at least 10 years away (Park’s TB of PSM,20th edition)

Developing any vaccine is hard

Can take 10-20 years to develop a product and cost hundreds of millions of dollars.

Phase 3 Phase 2b

Phase 1a, 2aPre-clinicalLaboratory

Phase 1b

Integrated Vector Control Management: Appropriate combination of one or more methods

I V C or

Environmental management

IEC, community participation,Intersectoral

cooperation ,etc

Integrated vector control programmeOne of the main strategy is to reduce the man-

mosquito contact.There are many methods to curb the mosquito

nuisanceNo single method of control is likely to provide a

solution in all situations.Integrated approach is the present trend to obtain

maximum results with the minimum effort and to avoid the excessive use of any one method, implement in an effective manner simultaneously.

Mosquito control measuresVarious methods are classified as bellow

I. Anti-larval methodsII. Anti-adult measuresIII. Protection against mosquito

bites

I. Anti-larval methods i) Environmental control ii) Chemical control III) Biological control

i) Environmental control

• Source reduction - elimination of breeding sites by minor engineering methods- yield permanent results

a. Filling and levelling-the filling of depressions holding water and the levelling of ground

b. Drainage -Designed to remove and dispose off excess or unwanted water.

Contd…

If anopheles are a problem• filling and drainage If Mansonia are a problem• Removal of aquatic plants to which larvae

attach themselves

Contnd… If Culex are a problem• Abolish domestic and peri domestic sources such as

cesspools and open ditches• Adequate collection, removal and disposal of sewage

and waste water If Aedes are a problem• Remove the water holding containers such as

discarded tins, empty pots, broken bottles, coconut shells and similar other artificial collections of water

ii) Chemical control

The commonly used larvicides are Mineral oils Paris green and Synthetic insecticides

Dosage Larvicide

Dosage

Temephos (Abate) 50-100 gm/ha

Fenthion (Baytex) 25-100 gm/ha

Chloropyrifos 10-15gm/ha

Use and limitations

• Useful in control of urban mosquitoes & in the presence of other refractory situations .

• Important limitations : Larvae not killed develop into adult mosquitoes. Repeated every 7 to 10 days Thorough knowledge about the habitats and ecology

of the target species. Environmental contamination.

III. Biological control• Control of mosquito breeding by application of

biological control systems.• An innovative approach to the problem of

mosquitoes and the diseases they transmit.• Cost effective, non-polluting, resistance does not

develop.• Mosquitoes can be controlled by employing their

natural enemies viz., fishes, bugs, nematodes, bacteria and fungi.

A female western mosquitofish, Gambusia affinis

The guppy (Poecilia reticulata), also known as the millionfish, one of the most popular freshwater aquarium fish species in the world.

Guppy fish

Contnd…

For maximum efficacy: Remove predacious fishes . Clean water of all vegetation. Shore line should be of clear grass Fishes should not be released in extremely shallow water. Tie nylon or brass mesh at the submerged end of inlet or

outlet pipes.

Biocides

• Bacillus sphaericus & Bacillus thuringiensis• Used only under special situations.• Used to kill mosquito larvae.• Breeding places:selective water bodies in

domestic and peri-domestic areas.• Should not be used for larval control in

potable water.

II. Anti-adult measuresVarious methods are classified as bellow

i. Indoor Residual spraysii. Space sprays-Foggingiii. Environmental sanitationiv. Genetic control

Daily mortality of 15 to 35% may be sufficient to cause an interruption of transmission.

Imagiciding has gradually replaced larviciding.

Insecticidal dosage for IRSInsecticide

preparation

Per sq. mtr

Rounds/yr

Area to be covered

DDT 50% 1 Kg/10ltr 1 gm 2 500sq.mtr

Malathion 25%

2 Kg/10ltr 2gm 3 250sq.mtr

Cyfluthrin 10%

125 gm/10ltr

25mg 2 500sq.mtr

III. Protection against mosquito bitesVarious methods are classified as bellow

i. Mosquito nets (Insecticide Treated bed Nets-ITNs) are distributed in high risk area

ii. Screeningiii. Repellents

In and out door fogging

Portable fogging machines to combat mosquitoes

Different types of foggers

Defined (WHO) as “the development of an ability in strain of insects to tolerate doses of toxicants” This is considered as one of the main obstacles to using insecticides which would prove lethal to the majority of individual in normal population of the same species”for vector control.This is due to biochemical and genetic factors.

Insecticide Resistance by vectors

III. Prersonal protection

Offers protection during sleep.

Material should be white to allow easy detection of mosquitoes

Top as well as sides of the net should be of netting

Best pattern is rectangular net

Size of the hole should not exceed 0.0475 inch in any diameter

No. of holes in one square inch is usually 150.

1) Mosquito net

2)Screening Screening of building with

copper or bronze gauge having 16 meshes to the inch is recommended

Costly but gives excellent results

Hole should not exceed 0.0475 inch in any diameter

3) Repellents• For application over the skin• Diethyl tolbutamine (Deet) is used• Found to be effective against C.fatigans for 18-20

hours.

Biological Control for Adults

Biological Control for LarvaePredacaeous diving beetle

Water Striders

Backswimmers

Dragonfly & Damselfly larvae

Thank you Any ????