Contents:

1. Introduction.

2. Life cycle.

3. Causes, incidence, and risk factors.

4. Symptoms.

5. Diagnosis and tests.

6. Complications.

7. Malaria Situation in Bangladesh.

8. Treatments.

9. References.

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Introduction:

Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases progressing to coma or death. It is widespread in tropical and subtropical regions, including much of Sub-Saharan Africa, Asia, and the Americas.

Five species of Plasmodium can infect and be transmitted by humans. Severe disease is largely caused by Plasmodium falciparum while the disease caused by Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae is generally a milder disease that is rarely fatal. Plasmodium knowlesi is a zoonosis that causes malaria in macaques but can also infect humans.

Malaria transmission can be reduced by preventing mosquito bites by distribution of mosquito nets and insect repellents, or by mosquito-control measures such as spraying insecticides and draining standing water (where mosquitoes breed). The challenge of producing a widely available vaccine that provides a high level of protection for a sustained period is still to be met, although several are under development. A number of medications are also available to prevent malaria in travelers to malaria-endemic countries (prophylaxis).

A variety of antimalarial medications are available. Severe malaria is treated with intravenous or intramuscular quinine or, since the mid-2000s, the artemisinin derivative artesunate, which is superior to quinine in both children and adults. Resistance has developed to several antimalarial drugs, most notably chloroquine.

There were an estimated 225 million cases of malaria worldwide in 2009. An estimated 781,000 people died from malaria in 2009 according to the World Health Organization's 2010 World Malaria Report, accounting for 2.23% of deaths worldwide.[9] Ninety percent of malaria-related deaths occur in sub-Saharan Africa, with the majority of deaths being young children. Plasmodium falciparum, the most severe form of malaria, is responsible for the vast majority of deaths associated with the disease. Malaria is commonly associated with poverty, and can indeed be a cause of poverty and a major hindrance to economic development.

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Life Cycle:

A female Anopheles mosquito carrying malaria-causing parasites feeds on a human and injects the parasites in the form of sporozoites into the bloodstream. The sporozoites travel to the liver and invade liver cells.

Over 5-16 days, the sporozoites grow, divide, and produce tens of thousands of haploid forms, called merozoites, per liver cell. Some malaria parasite species remain dormant for extended periods in the liver, causing relapses weeks or months later.

The merozoites exit the liver cells and re-enter the bloodstream, beginning a cycle of invasion of red blood cells, asexual replication, and release of newly formed merozoites from the red blood cells repeatedly over 1-3 days. This multiplication can result in thousands of parasite-infected cells in the host bloodstream, leading to illness and complications of malaria that can last for months if not treated.

Some of the merozoite-infected blood cells leave the cycle of asexual multiplication. Instead of replicating, the merozoites in these cells develop into sexual forms of the parasite, called male and female gametocytes, that circulate in the bloodstream.

When a mosquito bites an infected human, it ingests the gametocytes. In the mosquito gut, the infected human blood cells burst, releasing the gametocytes, which develop further into mature sex cells called gametes. Male and female gametes fuse to form diploid zygotes, which develop into actively moving ookinetes that burrow into the mosquito midgut wall and form oocysts.

Growth and division of each oocyst produces thousands of active haploid forms called sporozoites. After 8-15 days, the oocyst bursts, releasing sporozoites into the body cavity of the mosquito, from which they travel to and invade the mosquito salivary glands. The cycle of human infection re-starts when the mosquito takes a blood meal, injecting the sporozoites from its salivary glands into the human bloodstream

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Figure 1: Life cycle of the Malaria Parasite.

Causes, incidents, and risk factors:

Malaria is caused by a parasite that is passed from one human to another by the bite of infected Anopheles mosquitoes. After infection, the parasites (called sporozoites) travel through the bloodstream to the liver, where they mature and release another form, the merozoites. The parasites enter the bloodstream and infect red blood cells.

The parasites multiply inside the red blood cells, which then break open within 48 to 72 hours, infecting more red blood cells. The first symptoms usually occur 10 days to 4 weeks after infection, though they can appear as early as 8 days or as long as a year after infection. The symptoms occur in cycles of 48 to 72 hours.

Most symptoms are caused by:

1. The release of merozoites into the bloodstream

2. Anemia resulting from the destruction of the red blood cells

3. Large amounts of free hemoglobin being released into circulation after red blood cells break open

Malaria can also be transmitted from a mother to her unborn baby (congenitally) and by blood transfusions. Malaria can be carried by mosquitoes in temperate climates, but the parasite disappears over the winter.

The disease is a major health problem in much of the tropics and subtropics. The CDC estimates that there are 300-500 million cases of malaria each year, and more than 1 million people die from it. It presents a major disease hazard for travelers to warm climates.

In some areas of the world, mosquitoes that carry malaria have developed resistance to insecticides. In addition, the parasites have developed resistance to some antibiotics. These conditions have led to difficulty in controlling both the rate of infection and spread of this disease.

There are four types of common malaria parasites. Recently, a fifth type, Plasmodium knowlesi, has been causing malaria in Malaysia and areas of southeast Asia. Another type, falciparum malaria, affects more red blood cells than the other types and is much more serious. It can be fatal within a few hours of the first symptoms.

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Symptoms:

Anemia

Bloody stools

Chills

Coma

Convulsion

Fever

Headache

Jaundice

Muscle pain

Nausea

Sweating

Vomiting

Diagnosis and tests:

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Figure 3: Transfusing a child with severe anaemia due to Malaria

Figure 4: A patient suffering from jaundice due to severe malaria.

Figure 2: Symptoms of Malaria

In order to make a malaria diagnosis, the healthcare provider may ask a number of questions concerning:

Current symptoms

Medical conditions

Family medical history

Current medications

Recent travel history.

The healthcare provider will also likely perform a physical exam, looking for signs or symptoms of malaria. He or she may also order certain tests to help in diagnosing malaria or another condition.

The doctor may suspect malaria based on the patient's symptoms, and the physical findings at examination; however, to make a definitive diagnosis of malaria, laboratory tests must demonstrate the malaria parasites, or their components.

 The best test available to diagnose malaria is called a blood smear. In this test, malaria parasites can be identified by examining a drop of the patient's blood under the microscope, spread out as a "blood smear" on a microscope slide. Prior to examination, the specimen (blood) is stained to give to the parasites a distinctive appearance. There are other blood tests available that may be used along with a blood smear to confirm a malaria diagnosis.

A malaria diagnosis can be difficult to make, especially in areas where malaria is not very common. A number of other conditions share similar symptoms with malaria. Some of these conditions the healthcare provider will consider before diagnosing malaria include:

The flu (influenza)

Common cold

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Figure 5: Blood smear test

Meningitis

Typhoid fever

Dengue fever

Acute schistosomiasis (disease caused by worms)

Bacteremia/septicemia (infection in blood)

Hepatitis

Viral gastroenteritis (stomach flu)

Yellow fever (disease typically transmitted by mosquitoes).

Complications:

Malaria can be fatal, particularly the variety that's common in tropical parts of Africa. The Centers for Disease Control and Prevention estimate that 90 percent of all malaria deaths occur in Africa — most commonly in children under the age of 5.

In most cases, malaria deaths are related to one or more of these serious complications:

Cerebral malaria. If parasite-filled blood cells block small blood vessels to your brain (cerebral malaria), swelling of your brain or brain damage may occur.

Breathing problems. Accumulated fluid in your lungs (pulmonary edema) can make it difficult to breathe.

Organ failure. Malaria can cause your kidneys or liver to fail, or your spleen to rupture. Any of these conditions can be life-threatening.

Severe anemia. Malaria damages red blood cells, which can result in severe anemia.

Low blood sugar. Severe forms of malaria itself can cause low blood sugar, as can quinine — one of the most common medications used to combat malaria. Very low blood sugar can result in coma or death.

Recurrence may occur Some varieties of the malaria parasite, which typically cause milder forms of the disease, can persist for years and cause relapses.

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Table 1: Indicators of severe malaria and poor prognosis [1,3-5]

Manifestation Features

Initial World Health Organization criteria from 1990 [3]

1. Cerebral malaria: Unarousable coma not attributable to any other cause, with a Glasgow Coma Scale score ≤9; Coma should persist for at least 30 min after a generalized convulsion

2. Severe anemia Hematocrit <15% or hemoglobin < 50 g/l in the presence of parasite count >10000/µl

3. Renal failure Urine output <400 ml/24 hours in adults (<12 ml/kg/24 hours in children) and a serum creatinine >265 µmol/l (> 3.0 mg/dl) despite adequate volume repletion

4. Metabolic (Lactic) Acidosis/acidosis

Metabolic acidosis is defined by an arterial blood pH of <7.35 with a plasma bicarbonate concentration of <22 mmol/L; hyperlactatemia is defined as a plasma lactate concentration of 2-5 mmol/L and lactic acidosis is characterized by a pH <7.25 and a plasma lactate >5 mmol/L.

5. Pulmonary edema or acute respiratory distress syndrome (ARDS)

Breathlessness, bilateral crackles, and other features of pulmonary oedema. The acute lung injury score is calculated on the basis of radiographic densities, severity of hypoxemia, and positive end-expiratory pressure

6. Hypoglycemia Whole blood glucose concentration of less than 2.2 mmol/l (less than 40 mg/dl).

7. Hypotension and shock (algid malaria)

Systolic blood pressure <50 mmHg in children 1-5 years or <70 mm Hg in patients ≥5 years; cold and clammy skin or a core-skin temperature difference >100C

8. Abnormal bleeding and/or disseminated intavascular coagulation

Spontaneous bleeding from the gums, nose, gastrointestinal tract, retinal haemorrhages and/or laboratory evidence of disseminated intravascular coagulation.

9. Repeated generalised ≥3 generalized seizures within 24 hours

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convulsions

10. Haemoglobinuria Macroscopic black, brown or red urine; not associated with effects of oxidant drugs or enzyme defects (like G6PD deficiency)

Added World Health Organization criteria from 2000 [4]

11. Impaired consciousness Various levels of impairment may indicate severe infection although not falling into the definition of cerebral malaria. These patients are generally arousable

12. Prostration Extreme weakness, needs support

13. Hyperparasitemia 5% parasitized erythrocytes or > 250 000 parasites/µl (in nonimmune individuals)

14. Hyperpyrexia Core body temperature above 400C

15. Jaundice (Hyperbilirubinemia)

Serum bilirubin of more than 43m mol/l (2.5 mg/dl).

Other

16. Fluid and electrolyte disturbances [5]

Dehydration, postural hypotension, clinical evidence of hypovolemia

17. Vomiting of oral drugs Patients with persistent vomiting may have to be admitted for parenteral therapy.

18. Complicating or associated infections

Aspiration bronchopneumonia, septicemia, urinary tract infection etc.

19. Other indicators of poor prognosis [5]

Leukocyte count >12,000/cumm; high CSF lactate (>6 mmol/l)and low CSF glucose; more than 3-fold elevation of serum enzymes (aminotransferases); increased plasma 5'-nucleotidase; low antithrombin III levels; peripheral schizontemia; papilloedema/retinal oedema

20. Malarial Retinopathy A large, prospective autopsy study of children dying with cerebral malaria in Malawi found malarial retinopathy to be a

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better indicator of malarial coma. Similar retinopathy in an adult has also been reported.

Malaria situation in Bangladesh:

Malaria has been a major public health problem in Bangladesh. Approximately 33.6% of the total population are at risk of malaria Majority of malaria cases are reported from 13 out of the total 64 districts in the country. About 4 million populations living in 34 upazillas of eight of the thirteen districts live in the epidemic-prone border areas. Focal outbreaks occur every year, and the response to control the epidemic is inadequate. Malaria cases are grossly under-reported due to shortcomings in surveillance and information.

Country is reporting on average 50,000 confirmed malaria cases with around 70% of Pf cases (killer malaria) and 450 malaria deaths annually. The case finding is very poor and <2% population at risk of malaria screened every year. In 2008-09, with the help of Global funds enhanced surveillance and case finding activities including vector control through bednets and treatment through ACTs resulted in a increase in lab confirmed cases and significant decrease in malaria deaths . Country did not reaport any probable malaria case in 2009. Programme is promoting LLINs & ITNs amongst the community as a vector control measure in these areas which has increased tremendously in last few years. Total 2.57 million bednets (LLINS + ITNs) were distributed and 6.42 million people are covered by it. However, it’s coverage in high endemic districts ranges between 40% to 63%.

 

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Figure 6: : Trends of confirmed malaria cases in Bangladesh, 1970-2009

Figure 7: Distribution of ACT and Number of malaria deaths in Bangladesh, 2005-2009

Figure 8: 2Cumulative availability of effective LLINs & ITNs in Bangladesh, 2005-2009

 

Total financing for malaria in 2009 was approximately US$ 9.5 million, the main sources being the Government (US$ 555 000), the Global Fund (US$ 7.7 million), the World Bank (US$ 890 000) and WHO (US$ 230 000).

Figure 9: Availability of funds by Source in Bangladesh, 2006-2009

 

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Pogramme Goals and Targets:

To reduce malaria morbidity and mortality until the disease is no longer a public health problem in the country.

Targets Baseline data in 2005

2010

To provide early diagnosis and prompt treatment (EDPT) with effective drugs to 80% of malaria patients

40% 80%

To provide effective malaria prevention to 80% of population at risk

24% 80%

To strengthen malaria epidemiological surveillance system

60% 100%

To establish Rapid Response Team (RRT) at national and district levels and increase preparedness and response capacity for containment of outbreaks

80% 100%

To promote community participation, and strengthen partnership with private sector and NGOs for malaria control

25% 80%

 

Control strategy:

Malaria control activities are integrated with the general health services Active Case Detection (ACD) and Passive Case Detection (PCD) with laboratory diagnosis

Prompt treatment Case management of severe malaria and complicated cases in hospital. Vector control minimal, no IRS with DDT since 1993. SEAR working group recommendation on revised control strategy has been adopted Due to spread of chloroquine resistance, drug regimen has been revised and COARTEM

has been introduced by programme Strengthening programme management is of high priority

Best practices and success stories

Establishment of partnership with NGO consortium. Promotion and use of ITNs/LLINs Quality diagnosis using RDT and effective treatment using ACTs

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Issues and Challenges:

Inadequate access to treatment and

diagnostic facilities especially in the remote areas

Inadequate programme management capacity at various level and management of severe malaria in hospitals

Poor coverage of prevention and control methods (IRS, ITN/LLIN coverage still low) in the community

Referral system is weak and pre-referral treatment provisions are limited;

Optimum treatment of cases of severe malaria in different categories of hospitals are inadequate

Cross-border malaria at the Bangladesh India and Ban- Myanmar border

Partners and donors

WHO World Bank Global fund BRAC and 14 member NGO Consortium 4 Local NGOs in Chittagong Hill Tract (CHT)

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Treatments:

Preventing malaria - four steps

There is an ABCD for prevention of malaria. This is: Awareness of risk of malaria. Bite prevention. Chemoprophylaxis (taking antimalarial medication exactly as prescribed). Prompt Diagnosis and treatment.

Awareness of the risk of malaria:

The risk varies between countries and the type of trip. For example, back-packing or travelling to rural areas is generally more risky than staying in urban hotels. In some countries the risk varies between seasons - malaria is more common in the wet season. The main type of parasite, and the amount of resistance to medication, varies in different countries. Although risk varies, all travellers to malaria-risk countries should take precautions to prevent malaria.

The mosquitoes which transmit malaria commonly fly from dusk to dawn and therefore evenings and nights are the most dangerous time for transmission.

Bite prevention:

We can an effective insect repellent to clothing and any exposed skin. Diethyltoluamide (DEET) is safe and the most effective insect repellent and can be sprayed on to clothes. It lasts up to three hours for 20%, up to six hours for 30% and up to 12 hours for 50% DEET. There is no further increase in duration of protection beyond a concentration of 50%. When both sunscreen and DEET are required, DEET should be applied after the sunscreen has been applied. DEET can be used on babies and children over two months of age. In addition, DEET can be used, in a concentration of up to 50%, if anyone is pregnant. It is also safe to use if you are breast-feeding.

If we sleep outdoors or in an unscreened room, we should use mosquito nets impregnated with an insecticide (such as pyrethroid). The net should be long enough to fall to the floor all round your bed and be tucked under the mattress. We should check the net regularly for holes. Nets need to be re-impregnated with insecticide every six to twelve months (depending on how frequently the net is washed) to remain effective. Long-lasting nets, in which the pyrethroid is incorporated into the material of the net itself, are now available and can last up to five years.

If practical, we should try to cover up bare areas with long-sleeved, loose-fitting clothing, long trousers and socks - if we are outside after sunset - to reduce the risk of mosquitoes biting. Clothing may be sprayed or impregnated with permethrin, which reduces the risk of being bitten through our clothes.

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Sleeping in an air-conditioned room reduces the likelihood of mosquito bites, due to the room temperature being lowered. Doors, windows and other possible mosquito entry routes to sleeping accommodation should be screened with fine mesh netting. we should spray the room before dusk with an insecticide (usually a pyrethroid) to kill any mosquitoes that may have come into the room during the day. If electricity is available, we should use an electrically heated device to vaporize a tablet containing a synthetic pyrethroid in the room during the night. The burning of a mosquito coil is not as effective.

Herbal remedies have not been tested for their ability to prevent or treat malaria and are therefore not recommended. Likewise, there is no scientific proof that homoeopathic remedies are effective in either preventing or treating malaria, and they are also not recommended.

Antimalarial medication (chemoprophylaxis):

Antimalarial medication helps to prevent malaria. The best medication to take depends on the country you visit. This is because the type of parasite varies between different parts of the world. Also, in some areas the parasite has become resistant to certain medicines.

There is a possibility of antimalarials that we may buy in the tropics or over the Internet, being fake. It is therefore recommended that we obtain our antimalarial treatment from our doctor's surgery, a pharmacist or a travel clinic. Medications to protect against malaria are not funded by the NHS. We will need to buy them, regardless of where we obtain them.

The type of medication advised will depend upon the area you are travelling to. It will also depend on any health problems we have, any medication you are currently taking, the length of our stay, and also any problems we may have had with antimalarial medication in the past.

We should seek advice for each new trip abroad. Do not assume that the medication that we took for your last trip will be advised for your next trip, even to the same country. There is a changing pattern of resistance to some medicines by the parasites. Doctors, nurses, pharmacists and travel clinics are updated regularly on the best medication to take for each country.

We must take the medication exactly as advised. This usually involves starting the medication up to a week or more before you go on your trip. This allows the level of medicine in our body to become effective. It also gives time to check for any side-effects before travelling. It is also essential that we continue taking the medication for the correct time advised after returning to our home (often for four weeks). The most common reason for malaria to develop in travellers is because the antimalarial medication is not taken correctly. For example, some doses may be missed or forgotten, or the tablets may be stopped too soon after returning from the journey.

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Symptoms of malaria (to help with prompt diagnosis):

Symptoms are similar to flu. They include fever, shivers, sweating, backache, joint pains, headache, vomiting, diarrhoea and sometimes delirium. These symptoms may take a week or more to develop after you have been bitten by a mosquito. Occasionally, it takes a year for symptoms to develop.

This means that we should suspect malaria in anyone with a feverish illness who has travelled to a malaria-risk area within the past year, especially in the previous three months.

Special situations:

Pregnant women are at particular risk of severe malaria and should, ideally, not go to malaria-risk areas. Full discussion with a doctor is advisable if you are pregnant and intend to travel. Most antimalarial medications are thought to be safe to the unborn child. Some, such as mefloquine, should be avoided in the first twelve weeks of pregnancy.

Non-pregnant women taking mefloquine should avoid becoming pregnant. You should continue with contraception for three months after the last dose.

If you are given doxycycline and are also taking the combined oral contraceptive pill (COCP) or using the patch, then you should use alternative contraception for the first three weeks of taking the doxycycline. This is because doxycycline may interfere with the effectiveness of the COCP (or patch). After three weeks you will not need to use any additional contraception.

If you have epilepsy, kidney failure, some forms of mental illness, and some other uncommon illnesses, you may have a restricted choice of antimalarial medication. This may be due to your condition, or to possible interactions with other medication that we may be taking.

If we do not have a spleen (if you have had it removed) or our spleen does not work well, then we have a particularly high risk of developing severe malaria. Ideally, we should not travel to a malaria-risk country. However, if travel is essential, every effort should be made to avoid infection and we should be very strict about taking our antimalarial medication.

Travellers going to remote places far from medical facilities sometimes take emergency medication with them. This can be used to treat suspected malaria until proper medical care is available.

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References:

http://www.mayoclinic.com/health/malaria/DS00475/DSECTION=complications http://malaria.emedtv.com/malaria/malaria-diagnosis-p2.html http://www.malariasite.com/malaria/Complications2.htm http://en.wikipedia.org/wiki/Malaria http://www.patient.co.uk/health/Malaria-Prevention.htm http://www.google.com/imghp?hl=en&tab=wi

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