2.

MALARIA
1. WHO AND HOW?
The malaria it is considered the most important parasitic disease in the world.
- Mosquito - borne disease
- Transmitted by the bite of a female Anopheles spp. Mosquito.
- The most important parasitic disease in the world.
- Infected to those who are exposed by the mosquito and aren’t protected

The paradigm of poverty - related diseases.

There are 3 “actors”: mosquito, human and parasite. The mosquito, usually bites at nights.

Aetiology
Malaria belongs to the parasite from the Plasmodium genus.
there are five human species:
- P. falciparum
- P. vivax
- P. malariae
- P. ovale
- P. knowlesi

Cuando el mosquito te pica, los Plasmodium van hasta el hígado y allí se multiplican para luego ser
liberados a la sangre. Las huevas de los Plasmodium hacen todo su ciclo hasta infectar los eritrocitos
y provocar que sean disfuncionales, dando lugar a la anemia.

El parásito necesita un huésped y un hígado para completar el ciclo e infectar al huésped.

2. WHERE?
The 20 century, Malaria’s happened all around the world. In 2016 it is focused in the Amazonia area,
South Africa and South Asia. The deaths of malaria are concentrated in South Africa.
 How do we measure malaria transmission?
In relation to the vector (EIR) or to the human (incidence of malaria episodes)

Entomological inoculation rate (EIR): number of infective bites/person/year

- Holoendemic (high-transmission): EIR= 100 to 1000 (the most people infected are children
because later they develop immunity)
- Hiperendemic (“moderate transmission”): EIR= 10 to 100
- Low endemicity (“low transmission”): EIR: 1 to 10
- Unstable transmission: EIR<1

3. HOW MANY?
- In 2016 where 216 million cases of Malaria in 91 countries.
- Most of the 90% of all malaria deaths occur in Africa.
- Also, there was 446.000 death due to malaria that year.
- Since 2000 there are a > 60% reduction of malaria.
- More than 70% of all Malaria deaths occur in children <5 years of age (they haven’t the
immunity). Pregnant womens are considered the most vulnerable persons (they lose the
immunity).

> 80% of malaria cases stay at home.

There has been a very good progress in malaria control from 2000 to 2015. Malaria death rate
decrease 60% and the incidence rate decrease 37%.

4. CLINICAL MALARIA
Uncomplicated malaria
- Incubation period: between 8 and 30 days (shorter for P. falciparum and longer for P.
malariae. Longer Incub periods have been seen for certain strains of P. vivax).
- Febrile paroxysm: recurrent and intermittent fevers, related to the periodicity of the life cycle,
every 48h (“tertian”, faliciparum, vivax…), 72h (quartan, malariae).
- Unspecific symptoms, malaise, followed by an intense feeling of cold (<1h), with cills. Soon
after, beginninf of the febirile (or not) component, which can raise temps >40ºC and may last
6h. After this, drowsiness, and heavy sweating.
- In children, any other symptoms also common (cough, diarrhea, vomiting…)

Three main syndromes in children: coma, distress and anemia.

More frequently organ failure in adults: kidney, liver, multiorgan.
 Cerebral malaria
The clinical syndrome characterized by coma (not able to localiza a painful stimulus) lasting > 1h after
a convulsion or after correction of hypoglycaemia, in a patient with malaria parasites and for which
other causes of coma have been excluded (ex: meningitis).

Effects of Malaria in pregnancy

On the mother we have anemia and all the common signs. On newborn and infant health there are a
lot of infections.

Is not just about the mother, is about the health of the child, whose life expectancy can be reduced by
the disease of the mother.

Also can be congenital Malaria.

¿And what about Plasmodium vivax?

- There is increasing evidence regarding the potential of P. vivax, traditionally considered a
benign species, to cause severe or even lethal disease.
- Important to distinguish mono-infections with co-infections with P. falciparum.
- Important to exclude also other co-infections
- Are we witnessing a true increase in the incidence of severe vivax disease or only an
increase in ur diagnostic capacities?
- The increase in resistance to drugs also implies higher risks for patients.

→ Vivax can no longer be considered “benign” and needs to be treated more aggressively.

Diagnosis
All cases of suspected malaria should have a parasitological test (microscopy or Rapid Diagnostic test
(RDT) to confirm the diagnosis

Should make a blood test and analyse by microscope the morphology of the erythrocytes to confirm
the diagnoses.

5. CONTROL OF MALARIA: PREVENTION AND TREATMENT

Malaria control
Now based on 3 main fronts:
1. Reducing human-vector contact:
○ Insecticide-treated nets
2. Vector control:
○ Indoor residual spraying
○ Larvicines
○ Environmental management
3. Measures against the parasite
○ Drugs for treatment: artemisinin - combination treatment (ACTs).
○ Drugs for prevention. Recomendadas en embarazadas.
○ Short-term future: malaria vaccines.
The drugs against parasite are not the same as the drugs used to prevent the malaria.

Effective case management with anti-malarial drugs remains the cornerstone of malaria strategies. En
caso de que sospechemos de una infección de malaria tenemos que poner al paciente en tratamiento
lo antes posible, le daremos antipalúdicos.
1. Reducing contact between humans and vectors (mosquitos)
- Insect repellents. Only useful ones based on diethyltoluamide (Relec).
- Bednets and other materials impregnated with long lasting insecticides. Their objective is an
universal coverage and their currentñy target is children <5 years and pregnant women.

2. Vector control
Challenges:
- Resistance → The parasite became resistance to the insecticides
- Logistics
- Costs
- Sustainability
- Acceptability
- Environmental toxicity

3. Drugs
Uses of antimalarial drugs
● Treatment of malarial infections.
● Prevention of new infections and interruption of transmission
○ Continuous prophylaxis/seasonal malaria chemoprevention
○ Intermittent preventive treatment
○ Mass drug administration (in all its different formats). Antipalúdicos para toda la
población.

Drugs remain the pillars of malaria control and prevention.

For treatment usually you need to combine one artemether with another drug.

When you are infected by Plasmidium vivax or ovale you have to include primaquine in your
treatment.

2015
- 189 million bednets distributed in Africa. Children <5 sleeping under bednets:
- 2000: <2%
- 2015: 68%
- 116 million people protected through indoor residual spraying
- 392 million ACT treatments procured from manufacturers

6. CHALLENGES AHEAD
The (many) challenges
● Funding gaps
○ financing will need to triple from current levels.
○ Current annual spending: US$ 2.7 billion
○ Annual spending required by 2030: US$ 8.7 billion

● Coverage gaps
○ Approximately one in four children in sub-Saharan Africa are still living in a
household without at least one ITN or protection from IRS.
○ Approximately 60 million malaria cases go undiagnosed and untreated

● Biological challenges
○ Insecticide resistance
○ Drug resistance (area next to Cambodia, Thailand…)
Multi drug resistance
- P. falciparum resistance to artemisinins has been detected in 5 countries in the Greater
Mekong subregion.
- Chloroquine resistance in P. vivax has been confirmed in 10 countries

7. MALARIA ELIMINATION
Countries certified as malaria-free (1955-1987)
Certification of malaria elimination: countries that achieve at least 3 consecutive years of zero
indigenous cases are eligible to apply for a WHO certification of malaria-free status. Between 1955
and 1987, 22 countries and 2 territories received this WHO certification.

Countries certified as malaria-free (1987 - 2015)

We didn’t have any country achieving the elimination.
Zero indigenous cases: in 2014, 13 countries reported 0 indigenous cases of malaria. They are:
Argentina, Azerbaijan, Costa Rica, Georgia, Iraq, Kyrgyzstan, Oman, Paraguay, Sri Lanka, Syrian
Arab Republic, Tajikistan, Turkey and Uzbekistan.

What happens when we stop?

When the prevention program of malaria finished, the index of malaria prevalence increase again. The
prevention of this disease must be a continuous progress still their erraquidation, no only a minimum
period of time.

Future elimination targets

8. MALARIA VACCINES
- In 1979 had been started the cloning of the parasite’s CS gene.
- In 1987. Design of the vaccines. Experimental prototype.
- In 1992 appeared the first clinical trials in humans with an efficacy of 25%.
- In 2001 appeared a clinical trial in adults in Gambia.
- Vaccinated individuals: 250
- Efficacy: 34%
- Duration of protection: 15 weeks
- In 2004 appeared a clinical trial in children 1-4 years of age in Mozambique.
- Vaccinated individuals: 1857
- Efficacy: 30% clinical malaria and 50% severe malaria.
- In 2007. Proof of concept in newborns.
- Vaccinated individuals: 214.
- Efficacy: 66%.

A phase III clinical trial: 11 participating centers in 7 African countries, 16.000 childre.

Summary of Phase III trial initial results

- RTS,S reduced malaria burden by half in children aged 5-17 months over the first 12 months
of follow-up post-vaccination.
- Efficacy was highly significant and consistent across different analyses.
- RTS,S showed to have an acceptable safety profile.

Nowadays, the proposal is to pilot the implementation of the vaccine in 3 countries (Ghana, Kenya
and Malawi) in Africa, prior to massive deployment.

CONTROL OF MALARIA IN PREGNANCY