Malaria Case Definitions

	Introduction
	Malaria Transmission
	Morbidity and mortality
	Case definitions
	Drug resistance
	Entomology
	Parasitology

Introduction

Ninety-three (93%) of the population in the WHO African Region live in epidemic or endemic malaria areas. Malaria ranks among the top 5 most common causes of Outpatient attendance in most countries, and has been estimated to account for 30% of febrile illnesses in the endemic areas of the Region.

The clinical symptoms of malaria are mimicked by many other diseases. A clinical case definition may therefore be adequate for treating a patient, but may not be adequate for reporting. However, for us to be able to assess how well a patient has been diagnosed and managed, we need to have a standard definition of a case of malaria. This is even more critical for surveillance purposes as there is a need to look at trends over time in the same district/area. In addition, we need to be able to compare the incidence of malaria between districts of one country and between different countries in the region or beyond.

Ideally, a case definition must be sufficiently sensitive to identify most persons with the condition under surveillance, but sufficiently specific to exclude persons who do not have the condition. These characteristics together with the level of prevalence of the condition in the community and the available laboratory tests, determine the likelihood that the case which fits the case definition is a real case. In low prevalence areas, it is better to come up with a tight (narrow) case definition while a wider looser case definition can be used where malaria is more common.

It is expected that the case definition will be used by all health workers, from community health workers to the consultants in large tertiary hospitals. The definitions will especially be useful for surveillance (notification) purposes, but will also be useful as a guide to clinical diagnosis. With training, it is envisaged that the definitions will be used all the time.

Different aspects of malaria control may use different definitions of malaria. For example:

	clinical definitions for diagnosis
	epidemiological definitions for surveillance
	entomological for vector control
	meteorological for forecasting

back to top

Malaria Transmission

Endemic malaria
Low endemicity: a person may attain adolescence (10 years of age) or even adulthood (20 years) before infection is acquired.

Moderate endemicity: maximum incidence occurs in childhood and adolescence. But it is still not unusual for adulthood to be attained before acquiring infection.

High endemicity: by late infancy (6-11 months) or early childhood (1-4 years) practically all are infected. Little acute illness in adolescents and still less in adults.

Hyperendemicity: most individuals acquire infection in late infancy or the second year of life. Acute manifestations are less frequent in children over five years and unusual in adults

Malaria Epidemic
A malaria epidemic is the occurrence of malaria cases in excess of the number expected in a given place at a given time. This unexpected increase may therefore be superimposed on the expected seasonal variations.

Epidemics occur in populations where malaria was either previously absent or persisted at low or moderate endemic levels. They are characterised by high incidence among all ages.

Seasonal malaria cycles
These are fluctuations in occurrence of malaria by season. The season is usually determined by rainfall in tropical areas and by temperatures in sub-tropical and temperate areas.

Periodic malaria cycles
These are cycles that usually last between 8 and 10 years. They are usually determined by rainfall with amplified loss of immunity occurring in periods of low rainfall and, hence, low transmission.

Secular trends of malaria
Long term upward or downward trends in occurrence of malaria.

Stable malaria
High transmission with very little variation between the years. Collective immunity in the population is high. Epidemics are unlikely.

Unstable malaria
Transmission levels are low and vary from year to year. Collective immunity is low. There is a high potential for epidemics.

back to top

Indicators of Malaria Morbidity and Mortality

Malaria infection
Asymptomatic parasitaemia among those living in malaria endemic areas due to acquired immunity following repeated exposure to malaria infection.

Malaria incidence rate
The number of new malaria infections occurring in a given population unit (e.g. per 1,000) in a given time period (e.g. 1 year).

Malaria point prevalence
The proportion of a given population (e.g. infants, children, adults or all) infected with malaria parasite at a given point in time. It is often given as a percentage. Those infected with malaria parasite would include the asymptomatic and symptomatic ones.

Malaria-specific mortality rate
The number of malaria deaths in a time period (usually one year) in a population unit (usually 1000).

Malaria Hospital case fatality rate (HCFR) [= CFR of severe and complicated malaria]
The number of malaria inpatient deaths in a time period divided by the number of inpatient malaria cases in the same period. The ratio is usually multiplied by 100 to express it as a percentage. When case fatality rates are being cited this definition should be used rather than the one below.

Malaria case fatality rate (CFR) (General)
The number of malaria deaths in a time period divided by the number of malaria cases in the same period. The ratio is usually multiplied by 100 to express the CFR as a percentage.

back to top

Malaria Disease Case Definitions

General Malaria Case Definitions
Malaria is vector-borne disease caused by a protozoa parasite of the genus plasmodium and naturally transmitted to man by the female anopheles mosquito. It usually clinically presents with recurrent attacks of fever, rigors, anaemia, haemolytic jaundice and splenomegaly. It is usually easy to treat when patients present early for treatment and are properly managed, but can become complicated with a high fatality if treatment is sought late or the patient is not properly managed.

Suspected malaria
A person living in a defined malaria area or with a history of travel to a malaria within the past 6 weeks, who has an acute onset of fever.

Simple/clinical/probable/ malaria case
A person living in a defined malaria area or with a history of travel to a malaria areas within the past 6 weeks who presents with a clinical syndrome of malaria.

A patient with a clinical syndrome of malaria is a patient presenting with an acute onset of fever and any of the following symptoms or signs:

Laboratory confirmed/positive malaria
A person living in a defined malaria area or with a history of travel to a malaria area within the past 6 weeks who presents with any of the following:

Plus
Parasites demonstrated in a thick or thin blood film.

Severe/complicated malaria
A case of malaria which warrants hospital admission. The diagnosis has to be confirmed microscopically and may be accompanied by the following life threatening complications:

Cerebral malaria: impaired consciousness; psychosis, convulsions and coma
Severe haemolytic anaemia with Hb <8gm/dl
Acute renal failure
Sepsis
Pneumonia
Hyperparasitaemia
Hyperthermia

Indigenous malaria
Malaria acquired in areas of established transmission

Imported malaria
Malaria diagnosed in an area where transmission does not occur, due to the infection having been acquired during travel to a malaria area.

Introduced malaria
Malaria acquired in a non-malaria area from an imported malaria case.

Induced malaria
Malaria acquired through artificial means such as blood transfusion, use of syringes or intravenous drug use.

Clinical malaria death
Death of a patient suffering from symptoms and signs of suspected severe/complicated malaria.

Confirmed malaria death
Death of a patient suffering from symptoms and signs of severe/complicated malaria whose diagnosis was confirmed by microscopy.

back to top

Drug Resistance

In-vivo test
The test aims to determine the effect of a treatment on the parasitaemia (asexual forms) of a case of malaria infection, whether sick or not. It therefore gives information about the infection in the human host.

In-vitro
This test measures the effect of antimalarials on the development of the parasite in culture. It therefore gives information about the parasite.

Therapeutic/treatment failure
A case of uncomplicated malaria which has had a correctly administered correct course of antimalarial treatment, which presents at any time after 48 hours after the start of the treatment with fever not due to any other cause.

Early treatment failure (ETF)
Therapeutic response is classified as ETF if the patient develops one of the following conditions during the first three days of follow-up:
i. Development of danger signs or severe malaria on Day 1, 2 or 3 in the presence of parasitaemia.
ii. Fever on Day 2 with parasitaemia > of Day 0 count.
iii. Fever on Day 3 with the presence of parasitaemia.
iv. Parasitaemia on Day ³ 25% of count on Day 3.

Late treatment failure (LTF)
Therapeutic response is classified as LTF if the patient develops one of the following conditions during the follow-up period from Day 4 to Day 14:
i. Development of danger signs or severe malaria in the presence of parasitaemia on any day from Day 4 to Day 14, without previously meeting any of the criteria of ETF.
ii. Fever in the presence of parasitaemia on any day from Day 4 to Day 14,
without previously meeting any of the criteria of ETF.

Adequate clinical response (ACR)
Therapeutic response is classified as ACR if the patient shows one of the following conditions during the follow-up period (up to Day 14):
i. Absence of parasitaemia on Day 14 irrespective of presence of fever, without previously meeting any of the criteria for ETF or LTF.
ii. Absence of fever irrespective of the presence of parasitaemia, without previously meeting any of the criteria for ETF or LTF.

Laboratory confirmed drug resistance
A patient with laboratory confirmed malaria blood parasites after having received full, correct treatment at any time between 48 hours and 14 days after start of treatment in whom drug resistance is laboratory confirmed either using the in-vivo or in-vitro method.

Classification of in-vivo antimalarial resistance
In the 7-day test, parasitological examinations are carried out on days 0, 1, 2, 3, 4, 5, 6, and 7.

In the 28-day test, additional examinations are carried out up to day 28, at least on days 14, 21 and 28.

The results are expressed as being either:
S sensitive, i.e. parasitaemia disappears in less than 7 days and does not reappear before day 29, or R resistant.

The degrees of resistance are defined as:
RI: parasitaemia disappears in less than 7 days, but reappears before day 29;
RII: parasitaemia does not disappear in less than 7 days, but on day 2 (at 48 hours) the parasite density drops to 25% or less of what it was on day 0;
RIII: parasitaemia does not disappear in less than 7 days, and on day 2 (at 48 hours) the parasite density does not drop to 25% of what it was on day 0.

Note: Day 0 corresponds to the beginning of the treatment.
The 28 day test assumes that the case is not exposed to re-infection.

In-vitro antimalarial testing
A culture of malaria parasites (P. falciparum only) provided as a specimen of 10ml heparinised blood is used to test for sensitivity to antimalarial drugs. The test is carried out at increasing drug concentrations, and either percentage of trophozoites developing into schizonts after 24 hours is measured or the invasion of new erythrocytes after 48 hours is measure.

The result is expressed either as a proportion (or percentage) of isolates (the parasites of one case) that develop at the various concentrations, or as concentrations effective (ECs) against a given percentage (e.g. 90%) of parasites, concentrations being calculated on the basis of the results.

Congenital malaria
Malaria transmitted vertically from mother to child during pregnancy or child birth.

Relapse malaria
Recurrence of clinical symptoms, signs and parasitaemia ten days after complete clearance of the malaria.
back to top

6. Entomological definitions

Basic case reproduction rate (BCRR)
This is the mean number of new cases resulting from one human case before the case recovers, assuming all other people are non-immune and uninfected.
For example, with a BCCR of 5, 1 case will give rise to 5 cases in the next generation, and 25 cases in the succeeding generation.

If the BCCR falls below 1, the disease will die out. Hence, for malaria transmission to be stopped the BCCR must fall below 1. In endemic areas of Southern Africa the BCCR can be over 1000.

Anopheles mosquitoes
A genus of widely distributed mosquitoes comprising of around 350 species. The malaria parasite is transmitted to humans through the bite of female Anopheles mosquitoes. The most important Anopheles species in Southern Africa are An. gambiae complex (includes A. gambiae s.s. and An. Arabiensis) and An. funestus complex.

back to top

Parasitological Definitions

Plasmodium
Plasmodium is a genus of protozoan parasites that live within the red blood cells of humans. The parasite undergoes its asexual development in humans and completes the sexual phase of its development in the stomach and digestive glands of an Anopheles mosquito.

Plasmodium species
There are four species of Plasmodium that cause human malaria: P. vivax, P. ovale, P. malariae and P. falciparum. In the absence of other complicating factors, acute severity and mortality occur almost exclusively in P. falciparum infections. In Southern Africa P. falciparum is the predominant species.

Minimum temperature for P. falciparum development
The development of P. falciparum in the female adult Anopheles mosquito requires a minimum temperature of 19°C. Above this temperature, the development of the parasite in the vector quickens. The duration of sporogony at optimum temperatures for P. falciparum is 8-10 days.

back to top