Symptoms Of Malaria

The symptoms of malaria appear 10 days to 4 weeks after the bite of infected mosquito, occurring as early as 8 days or as long as an year after the infection. The three causes for appearance of symptoms are- The release of merozoites into the bloodstream, anaemia (due to destruction of the RBCs) and release of large amount of free hemoglobin into circulation after RBC's break open. (http://www.nytimes.com/)

A) UNCOMPLICATED MALARIA
The clinical symptoms of malaria are as follows:-
' Fever (the cardinal symptom of malaria)
' Headache
' Cough
' Fatigue
' Malaise
' Shaking chills
' Arthralgia
' Myalgia
' Nausea and vomiting
' Diarrhea
' Jaundice
Delay in treatment can lead to kidney failure, mental confusion, seizures, coma and death. General debility, anaemia or clogging of the vessels of cerebral tissues by affected red blood cells may also contribute to death. However, complications of severe anaemia and cerebral malaria are thought to be the major cause of morbidity and mortality (Perlmann et al.,2002)
Malaria typically produces a string of recurrent attacks, or paroxysms, which subside in a few weeks without treatment in case of P.vivax malaria and is likely to be lethal without treatment in case of P.falciparum (Understanding malaria, NIAID, 2007). The paroxysm usually begins in afternoon and lasts 8-12 hours.
Table 2.3: Three successive stages of uncomplicated malaria
Stage 1

(COLD STAGE) Stage 2

(HOT STAGE) Stage 3

(SWEATING STAGE)
Symptoms
Shivering(rigor) and feeling of intense cold, teeth chattering, dry and pale skin, vomiting, lips and fingers become cyanotic Skin is dry & burning, intense headache, intense thirst, nausea and vomiting are less common, temperature 106??F or more Drenching sweat, patient feeling tired & weak, is likely to fall asleep, temperature falls rapidly
Duration 15 minutes-1 hour 2-6 hours 2-5 hours

B) SEVERE MALARIA
Clinical manifestations of severe malaria is age dependent and results from products of erythrocytic schizogony like malaria pigments, endogenous pyrogens, parasite debris and merozoites. Complicated infections like serious organ failures or abnormalities in the patient's blood or metabolism are the cause of severe malaria. Being medical emergency severe malaria should be treated aggressively.
Details regarding manifestations of severe malaria are given below-
' Cerebral malaria- marked by seizures and abnormal behaviour. It is a frequent feature of severe malaria that occurs in all ages and has a fatality rate of 20% despite of treatment.
' Severe anaemia- due to accelerated destruction of red blood cells. It is more common in children and characterized by respiratory distress.
' Metabolic acidosis- marked by excessive acidity in the blood and tissue fluids, it is an important cause of death from severe malaria.
' Hypoglycemia (low blood glucose) - occurs due to failure of hepatic glucogenesis and glycogenolysis. Also it may occur in pregnant women with uncomplicated malaria.
' Renal failure- common complication of severe P.falciparum malaria, resulting from hemoglobin deposition in renal tubules.

2.9 Vector control
The two key measures of malaria control today are treating the disease in humans and attacking the vector. Although antimalarial drugs have been known since the days of herbalists, many of them are now ineffective as the pathogen has evolved drug resistance (Godfray, 2013). Currently, the major strategies for vector control include environmental management, use of insecticide-treated (bed) nets (ITNs) and indoor residual spraying (IRS).

a) Environmental management

For effective control of malaria, it is crucial to halt the further breeding of Anopheles mosquitoes. Some simple measures that could be undertaken to manage the environment include:-
' Source reduction by filling ditches, pits, waste disposal and sanitation
' Creating canals to improve water flow
' Draining empty tins, car tires, fridges, vehicle etc to prevent breeding of other types of mosquitoes
' Planting shaded trees near potential anopheles larval breeding habitats

b) Insecticide-Treated Nets (ITNs)
Insecticide-impregnated materials like bed nets and curtains are effective for protecting individuals from bite of Anopheles at night. Pyrethroids are the only insecticides implemented for impregnation of bed nets due to their low mammalian toxicity and rapid knock-down effect on vectors at low doses. More recently, long-lasting insecticide-treated nets (LLIN) have been developed that may remain active for five years.

c) Indoor Residual Spraying (IRS)
Indoor residual spraying (IRS) is the chemical control measure which results in the death of mosquitoes, often as they rest up after feeding. They have been applied as long lasting chemical insecticides on the walls and roofs of all houses and domestic animal shelters in a given area. Broader range of insecticides can be used like DDT is still widely employed, especially where people live in unplastered huts.

Figure 2.5: Indoor residual spraying (IRS) for control of malaria
(Source: http://www.agfax.net/radio/detail.php?i=333&s=t)
2.10 National Drug Policy on Treatment of Malaria
National Vector Borne Disease Control Programme (NVBDCP), the central nodal agency in India is responsible for providing the guidelines for malaria treatment. The National Drug Policy on Malaria came into existence in 1982 and has subsequently been reviewed and revised periodically. Under the National Drug Policy effective treatment of malaria aims to provide complete cure of malaria cases, prevent the progression of uncomplicated malaria into severe malaria, prevent relapses by administration of radical treatment and interruption of transmission of malaria by use of gametocytocides.
A) TREATMENT OF UNCOMPLICATED MALARIA
Malaria is entirely preventable and curable disease. Strenuous efforts are being made to develop new procedures for malaria treatment and control. The treatment depends on the severity of the infection, the age of patient, the degree of background immunity, the likely pattern of susceptibility to antimalarial drugs and the cost and availability of such drugs. The uncomplicated malaria is defined as symptomatic malaria, without signs of severity or evidence of vital organ dysfunction. The objective of treating uncomplicated malaria is to cure the infection (elimination of illness causing parasites from the body) and to prevent the emergence and spread of resistance to antimalarials.

' Treatment of P. vivax malaria
The confirmed P.vivax cases should be treated with chloroquine in full therapeutic dose of 25 mg/kg divided over three days. Vivax malaria relapses due to the presence of hypnozoites, which remain dormant in liver cells. In India, the relapse rate in vivax malaria is around 30%. Therefore, for its prevention, primaquine should be given at a dose of 0.25 mg/kg daily for 14 days under supervision. However, primaquine is contraindicated in G6PD deficient patients, pregnant women and infants as it can lead to hemolysis in such patients. If the patient develops symptoms like dark coloured urine, abdominal pain, yellow conjunctiva, nausea and vomiting, he/she should be adviced to stop primaquine immediately and consult the doctor.
' Treatment of P. falciparum malaria
Combination of drugs having different modes of action, is now the preferred approach to treat malaria in order to inhibit the emergence and spread of parasites resistant to one component of the combination (Greenwood et al.,2005). Artimisinin Combination Therapy (ACT) should be given to all confirmed P.falciparum cases, accompanied by a single dose of primaquine (0.75mg/kg body weight) on day 2.
Artemisinin and its derivatives (artesunate, artemotil (arteether), artemether, dihydro-artemisinin) causes rapid clearance of parasitaemia and resolution of symptoms. ACT consist of an artemisinin derivative (given above), combined with a long acting antimalarial (amodiaquine, mefloquine, lumefantrine orsulfadoxine-pyrimethamine). ACTs prevent the gametocyte development thereby reducing malaria transmission (Guerin et al.,2002). The recommended ACT in the National Programme of India is artesunate (4 mg/kg body weight) that is to be given daily for 3 days and sulfadoxine (25 mg/kg body weight) -pyrimethamine (1.25 mg/kg body weight) on Day 0. Presently, the registered fixed dose combinations available in market are:- artemether-lumefantrine, artesunate- amodiaquine and blister pack of artesunate- mefloquine.
Oral Artemisinin monotherapy for uncomplicated malaria is banned in India since it can lead to development of drug resistance due to its rapid action.

' Treatment of malaria in pregnancy
Malaria infection during pregnancy poses substantial risks to the pregnant woman and her fetus. It may lead to spontaneous abortion, stillbirth, pre-maturity and low birth weight. For treatment of P. falciparum malaria in second and third trimesters of pregnancy, ACT is recommended, while quinine is recommended in the first trimester. Treatment of P.vivax malaria is done with chloroquine.

B) TREATMENT OF SEVERE MALARIA
The primary objective of treatment of severe malaria is to save the life of patient. Prevention of recrudescence, transmission or emergence of resistance and complications are the secondary objectives. Foetal and maternal complication involved in pregnancy with severe malaria acquires prompt attention. Severe manifestations in P. falciparum infection over a span of 12 ' 24 hours may lead to death, if not treated straightaway.
The following features characterize severe malaria-
' Impaired consciousness/coma
' Renal failure (Serum Creatinine >3 mg/dl)
' Severe anaemia (Hb <5 gm/dl)
' Abnormal bleeding and Disseminated intravascular coagulation (DIC)
' Hyperparasitaemia (>5% parasitized RBCs )
' Hyperpyrexia (Temperature >106??F or >42??C)
' Pulmonary oedema/acute respiratory distress syndrome
' Repeated generalized convulsions

Parental artemisinin derivatives or quinine are adviced for treatment of severe malaria.

Artesunate: It is a rapidly acting drug, which is given intravenously or intramuscularly (2.4 mg/kg body weight) at the time of admission, then at 12 hours and 24 hours and then once a day.

Quinine: 20 mg quinine salt/kg body weight on admission (intravenous infusion in 5% dextrose/dextrose saline over a period of 4 hours) followed by maintenance dose of 10 mg/kg body weight 8 hourly is recommended. Bolus injection of quinine should never be given

??-?? Arteether: A dose of 150 mg is given intramuscularly, daily for 3 days in adults. However, it is not recommended for children.

Artemether: 3.2 mg/kg body weight is given on admission intramuscularly, followed by 1.6 mg/kg body weight per day.
After taking oral therapy, further follow-up treatment should be given as follows-Patients receiving parenteral quinine should be treated with oral quinine 10 mg/kg body weight three times a day to complete a course of 7 days, along with doxycycline 3 mg/ kg body weight per day for 7 days. Since doxycycline is contraindicated in pregnant women and children under 8 years of age; instead, clindamycin with a dose of 10 mg/kg body weight 12 hourly should be used for 7 days (Guidelines for diagnosis and treatment of Malaria 2011. 2nd edition)

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