Malaria

is a vector-borne infectious disease caused by protozoan parasites. Malaria has infected humans for over 50,000 years, and may have been a human pathogen for the entire history of our species. It causes about 400–900 million cases of fever and approximately one to three million deaths annually. This represents at least one death every 30 seconds. If the prevalence of malaria stays on its present upwards course, the death rate could double in the next twenty years.

The

term malaria originates from Medieval Italian: mala aria — “ bad air"; and the disease was formerly called ague or marsh fever due to its association with swamps over 40% of the population lives in areas where malaria transmission occurs (i.e., parts of Africa, Asia, the Middle East, Central and South America, Hispaniola, and Oceania).
Source: WHO, 2003

The primary vector species are A. culicifacies and
A. stephensi. In most parts of the country, the transmission occurs post-monsoon, between July and November

1998

2001

2002

2003

1999

2000

Sindh

Roll Back Malaria Monitoring and Evaluation Generated:4/27/2005

2003 2002

Baluchistan

2003 2002

2003 2002
NWFP

2003 2002
FATA

Punjab

2003 2002

PATHOGENESIS

Plasmodium species which infect humans Plasmodium vivax (tertian) Plasmodium ovale (tertian) Plasmodium falciparum (tertian) Plasmodium malariae (quartan)

Malaria Life Cycle

Sporogony
Oocyst Sporozoites Mosquito Salivary Gland

Zygote

Gametocytes

Exoerythrocytic (hepatic) cycle

Hypnozoites (for P. vivax and P. ovale)

Merozoites
Erythrocytic Cycle

Schizont

preerythrocytic sporogony

Schizogony

Schizont Merozoites Trophozoites

Some characteristics of infection with four species of human Plasmodia
P.v.
Incubation period (days) Erythrocytic cycle (hours) Primary attack Febrile paroxysms (hours) Relapses

P.o. 17 (16-18) or longer 50 Mild

P.m. 28 (18-40) or longer 72 Mild

P.f. 12 (9-14) 48 Severe in nonimmunes 16-36 or longer -

15 (12-17) or up to 612 months 48 (about) Mildsevere 8-12 ++

8-12 ++

8-10 -

Schizogenic periodicity and fever patterns
• Schizogenic periodicity is length of asexual erythrocytic phase – 48 hours in P.f., P.v., and P.o. (tertian) – 72 hours in P.m. (quartan) • Initially may not see characteristic fever pattern if schizogeny not synchronous • With synchrony, periods of fever or febrile paroxsyms assume a more definite 3 (tertian)- or 4 (quartan)- day pattern

Malaria Diagnosis
• • • • • • Clinical Diagnosis Malaria Blood Smear Fluorescent microscopy Antigen Detection Serology Polymerase Chain Reaction

Malaria Clinical Diagnosis
• Early symptoms – Headache – Malaise – Fatigue – Nausea – Muscular pains – Slight diarrhea – Slight fever, usually not intermittent • Could mistake for influenza or gastrointestinal infection

Malaria Clinical Diagnosis
• Signs – Anemia – Thrombocytopenia – Jaundice – Hepatosplenomegaly – respiratory distress syndrome – renal dysfunction – Hypoglycemia – Mental status changes

Malarial Clinical Diagnosis, Paroxysm
– Slight fever may worsen just prior to paroxysm • Paroxysm – Cold stage - rigors – Hot stage – Max temp can reach 40-41o C, splenomegaly easily palpable – Sweating stage – Lasts 8-12 hours, start between midnight and midday

Malaria Lab Diagnosis
Blood Smear
• Remains the gold standard for diagnosis • Giemsa stain • distinguishes between species and life cycle stages • parasitemia is quantifiable • Threshold of detection • thin film: 100 parasites/l • thick film: 5 -20 parasites/l

Schizont

Ring form

Gametocytes

Trophozoite

Malaria Antigen Detection
• Immunologic assays to detect specific antigens • Commercial kits now available as immunochromatographic rapid diagnostic tests (RDTs), used with blood -P. falciparum histidine-rich protein 2 (PfHRP-2) -parasite LDH (pLDH) • Cannot detect mixed infections • Cross reactivity with rheumatoid factor reportedly corrected

RBM Partnership Secretariat, Malaria Medicines & Supplies Services Copenhagen – 31 January 2006

Malaria distribution and reported case of resistance or treatment failure

Malaria diagnosis
Parasitological confirmation (microscopy or RDT) before treatment Exceptions: – children under 5 years of age, from areas of high transmission where treatment is based on clinical diagnosis – suspected severe malaria where parasitological confirmation is not immediately possible

Changing antimalarial treatment policy
• Treatment failure of >10% (as assessed through monitoring of therapeutic efficacy at 28 days) • New treatment – an average cure rate of > 95% as assessed in clinical trials

Treatment of uncomplicated falciparum malaria
Artemisinin-based combination therapies (ACT) are the treatments recommended for all cases of uncomplicated falciparum malaria including: – in infants, – in people living with HIV/AIDS – for home-based management of malaria – pregnant women in the 2nd and 3rd trimesters Exception: • 1st trimester of pregnancy

Treatment of uncomplicated falciparum malaria
First-line treatment: • The following ACTs are presently recommended: – artemether-lumefantrine – artesunate + amodiaquine – artesunate + mefloquine – artesunate + sulfadoxine-pyrimethamine • Efficacy of ACTs depend on the efficacy of the partnermedicine The artemisinin derivatives (oral formulations) and partner medicines of ACTs are not recommended as monotherapy

Artemether-lumefantrine
Currently available as co-formulated tablets > 14 Yrs containing Tab. Artem DS plus 2+0+2 (for 3 days) 120 mg of 20 mg of artemether and lumefantrine. 3-8 recommended treatment is a 6-dose The total Yrs Tab. Artem DS plus 1+0+1 (for 3 regimen of artemether-lumefantrine days) a day for 3 twice days.

Treatment of uncomplicated falciparum malaria
Second-line treatment: – alternative ACT – quinine + tetracycline or doxycycline or clindamycin

Artesunate (2 mg/kg OD)+ tetracycline (4 mg/kg 6 hourly) Artesunate (2 mg/kg OD)+ doxycycline (3.5 mg/kg OD) Artesunate (2 mg/kg OD)+ clindamycin (10 mg/kg BD). Quinine (10 mg salt/kg three times a day) + tetracycline Quinine (10 mg salt/kg three times a day) + doxycycline Quinine (10 mg salt/kg three times a day) + clindamycin.

Any of these combinations to be given for 7 days

Treatment of severe falciparum malaria
Any of Inj. Artem 80 mg I/M 2 stat then the following antimalarial medicines are recommended Inj. Artem 80 mg I/M x OD for 4 days – Artesunate i.v. or i.m – artemether i.m. – quinine (i.v. infusion or i.m. injection).

Full course of ACT or quinine + clindamycin or doxycycline when patient can tolerate oral treatment

Treatment of Plasmodium Vivax & Ovale Infection
Tab. Nivaquine 4 stat then 2 after 6 hrs. then 1+0+1 for next two Chloroquine phosphate days (total 10 tab.) 1 Gm stat, followed by 500 + Tab. Primaquine 30mg 1xOD for 14 days mg at 6, ______________________________________ base 24 & 48 hours + Primaquine 30 mg >14 Yrs daily for 14 days. ( provided G6PD normal) Tab. Artem DS plus 2+0+2 (for 3 days) + Tab. Primaquine 30mg 1xOD for 14 days

Where ACT has been adopted as the first-line treatment 3-8 Yrs falciparum malaria, it may also be for P. used for Tab. Artem DS plus 1+0+1 (for 3combination with P. vivax malaria in days) + Tab. Primaquine 30mg 1xOD for 14 days primaquine for radical cure.

Approaches That Should Be Avoided
• Partial treatments should not be given even when patients are considered to be semi-immune or the diagnosis is uncertain. • A full course of effective treatment should always be given once a decision to give antimalarial treatment has been reached. • The artemisinins and partner medicines of ACTs should not be available as monotherapies.

Malaria Vaccine
An effective vaccine
against malaria has been developed and could be licensed by 2010.
(BBC NEWS 15 October 2004)

The research is very high
quality and the findings are very encouraging.
(Allan Shapira of Roll Back Malaria)

We believe a malaria
vaccine, even of moderate efficacy, could make a huge impact. (Lead researcher Professor
Pedro Alonso)

CONTACT: alauddinsarwar@gmail.com doctoralauddin@yahoo.co.in

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