Plasmodium falciparum: Infectious substances pathogen safety data sheet

Section I: Infectious agent

Name

Plasmodium falciparum

Agent type

Parasite

Taxonomy

Family

Plasmodiidae

Genus

Plasmodium

Species

falciparum

Synonym or cross-reference

Malaria, Falciparum malaria, Malignant tertian^{Footnote 1},^{Footnote 2},^{Footnote 3}, Laverania (subgenus of Plasmodium)^{Footnote 4},^{Footnote 5}.

Characteristics

Brief description

P. falciparum is a unicellular protozoan parasite. Cells contain a DNA genome 22.8 Mb in length and arranged in 14 chromosomes^{Footnote 6}. Morphological characteristics of P. falciparum vary greatly according to the life-cycle stage^{Footnote 7}. The most clinically relevant are the blood-stage forms of P. falciparum including merozoites, ring-stage trophozoites, and gametocytes. Merozoites are approximately 1.5 μm by 1 μm in diameter and produce a large vacuole, giving cells a ring-like appearance as they develop into trophozoites^{Footnote 7}. Gametocytes are elongated and crescent-shaped, measuring approximately 8-12 μm by 3-6 μm^{Footnote 7},^{Footnote 8}.

Properties

P. falciparum has multiple life-cycle stages and can reproduce sexually and asexually. P. falciparum sporozoites are injected into the skin of a host through a mosquito's proboscis when it takes a blood meal^{Footnote 9}. Sporozoites migrate to the host liver where they establish infection in hepatocytes and develop into merozoites^{Footnote 9}. Merozoites are released into the bloodstream where they reproduce asexually within infected host red blood cells^{Footnote 10}. Merozoites can then either develop into trophozoites, which become part of a Schizont (cluster of daughter parasites), or differentiate into gametocytes (male or female)^{Footnote 10}. Erythrocytes containing Schizonts rupture, releasing merozoites that can infect other erythrocytes. The gametocyte form remains within the erythrocyte and can be transmitted to mosquitoes, where sexual reproduction occurs^{Footnote 11}. Gametocytes in the mosquito egress from erythrocytes and develop into gametes that combine to form a zygote, which eventually develops into an oocyst that releases infectious sporozoites^{Footnote 9}.

Plasmodium spp. have a specialized apical complex that is involved in invasion of erythrocytes^{Footnote 9}. Virulence factors in P. falciparum include PfEMP1 and rifin proteins^{Footnote 12},^{Footnote 13}.

Section II: Hazard identification

Pathogenicity and toxicity

Clinical presentations of P. falciparum-associated malaria can range from asymptomatic to mild to severe^{Footnote 2},^{Footnote 14}. Symptoms of mild, uncomplicated malaria include fever, chills and sweats, headache, muscle/joint pain, vomiting, and diarrhoea^{Footnote 2},^{Footnote 15},^{Footnote 16}. After 1 to 3 days of mild symptoms, disease may become more severe. Symptoms of severe malaria in adults include jaundice (40-70%), seizures (20%), impaired consciousness, pulmonary oedema, acidosis, and organ dysfunction^{Footnote 17},^{Footnote 18}. Children with severe malaria may present with impaired consciousness, seizure (60-80%) and coma (cerebral malaria), respiratory distress (acidosis), severe anaemia (20-50%), and hypoglycaemia (30%)^{Footnote 18}. Cerebral malaria is relatively uncommon in adults and affects about 1% of children with P. falciparum malaria^{Footnote 13}. Cerebral malaria is characterised by retinopathy, altered consciousness, seizure and coma^{Footnote 13},^{Footnote 18}. With available treatment, estimated mortality rates for uncomplicated and severe malaria are 0.1% and 15-20% respectively^{Footnote 17},^{Footnote 18}. For severe malaria, more than 50% of deaths occur with 24 hours of hospital admission^{Footnote 17},^{Footnote 18},^{Footnote 19}.

Approximately 11% of children that recover from cerebral malaria develop neurological sequelae including hemiparesis (4.4%), quadriparesis (3.5%), impaired hearing, vision, speech (2%), and epilepsy^{Footnote 18}.

Epidemiology

The World Health Organisation (WHO) defines 5 global regions with malaria-endemic countries: Africa, South-East Asia, Eastern Mediterranean, Western Pacific, and the Americas^{Footnote 25}. Malaria is endemic in approximately 80 countries^{Footnote 25}.

In 2017, approximately 219 million cases of malaria occurred worldwide^{Footnote 25}. The incidence rate of malaria varies according to region; incidence rates globally and in Africa are approximately 59 and 219 cases per 1,000 population at risk, respectively^{Footnote 25}. Typically, 92% of malaria cases occur in Africa, 5% in South-East Asia, and 2% in the Eastern Mediterranean^{Footnote 25}. P. falciparum accounts for over 90% of malaria cases globally, and causes approximately 99.7% of malaria cases in Africa, 63% in South-East Asia, 69% in Eastern Mediterranean, 72% in Western Pacific, and less than 26% in the Americas^{Footnote 25}. Transmission intensity and seasonality vary geographically^{Footnote 26},^{Footnote 27}.

The WHO estimated 435,000 malaria deaths occurred globally in 2017^{Footnote 25}. In 2017, an estimated 93% of malaria deaths occurred in Africa^{Footnote 25}; P. falciparum accounts for the vast majority of malaria-related mortality^{Footnote 28}. Increased availability and use of rapid diagnostic testing and artemisinin-based therapies have contributed to a decrease in malaria deaths. Estimated deaths per 100,000 population at risk in Africa and globally in 2017 were 44.1 and 11.7, respectively^{Footnote 25}. Children under 5 years of age accounted for an estimated 61% of malaria deaths in 2017^{Footnote 25}.

Vector control measures (e.g., insecticide-treated mosquito bed nets, indoor residual spraying) have reduced global incidence of malaria substantially^{Footnote 25},^{Footnote 28}. Between 2005 and 2017, incidence and mortality of P. falciparum-associated malaria was reduced by approximately 28% and 43%, respectively^{Footnote 28}. However, vector resistance to pyrethroid insecticides used in bed nets and for indoor residual spraying has become widespread^{Footnote 25}.

Approximately 30,000 travel-related cases of malaria are reported globally each year^{Footnote 29}.

Children under 5 years of age, pregnant women, and individuals who are co-infected with HIV have a higher risk of severe disease^{Footnote 2},^{Footnote 17},^{Footnote 18},^{Footnote 20}.

Host range

Natural host(s)

Humans (intermediate host), some species of female Anopheles mosquitoes^{Footnote 14}.

Other host(s)

Non-human primates have been experimentally infected^{Footnote 30}.

Infectious dose

Unknown.

Incubation period

Usually 7 to 27 days (median 13 days) and 8 to 29 days (median 16 days) for mosquito-transmitted and transfusion-transmitted P. falciparum-associated malaria, respectively^{Footnote 21}.

Communicability

Malaria caused by Plasmodium spp. is primarily transmitted to humans by mosquito vectors. Malaria transmission via blood transfusion is relatively rare in non-endemic areas^{Footnote 21}. Between 2010 and 2015, 8 transfusion-transmitted cases were reported among non-endemic countries and only one of these cases was caused by P. falciparum.^{Footnote 21} In some malaria-endemic areas, where the prevalence of Plasmodium spp. in donor blood can be as high as 55%^{Footnote 22}, risk of transfusion-transmitted malaria is considerably higher despite screening methods. Transmission of P. falciparum via solid organ transplantation is rare^{Footnote 23}. Vertical transmission of P. falciparum has been described^{Footnote 24}.

Section III: Dissemination

Reservoir

Asymptomatic humans infected with P. falciparum^{Footnote 14},^{Footnote 31}. African apes have also been identified as a reservoir^{Footnote 5}.

Zoonosis

None.

Vectors

More than 40 species of female Anopheles mosquitoes are malaria vectors, with A. gambiae being the dominant vector species^{Footnote 2},^{Footnote 32}. The sexual-stage form of P. falciparum develops into an infectious sporozoite in the mosquito. Infected mosquitoes transfer sporozoites to humans when taking a blood meal. P. falciparum-infected humans can transfer gametocytes to uninfected mosquitoes; however, less than 50% of mosquitoes that feed on an infected host become infected^{Footnote 33}.

Section IV: Stability and viability

Drug susceptibility/resistance

Aminoquinolines (e.g., chloroquine, amodiaquine, primaquine, piperaquine); arylaminoalcohols (e.g., quinine, mefloquine, lumefantrine, halofantrine); naphthoquinone/antifolate (e.g., atovaquone/proguanil); artemisinins (e.g., artemether, artesunate, dihydroartemisinin, artemisinin, arteether); antifolates (e.g., pyrimethamine, cycloguanil); pyronaridine; sulfonamides (e.g., sulfadoxine) and sulfones; and antibiotics (e.g., tetracycline, azithromycin, clindamycin, doxycycline) have been used to treat P. falciparum-associated malaria^{Footnote 17},^{Footnote 34},^{Footnote 35},^{Footnote 36}.

P. falciparum resistance to chloroquine, mefloquine, halofantrine, lumefantrine, pyrimethamine, cycloguanil, chlorcycloguanil, atovaquone, and sulfonamides and sulfones has been documented^{Footnote 17},^{Footnote 34},^{Footnote 35}. P. falciparum resistance to artemisinin-based combination therapies is emerging in Southeast Asia^{Footnote 35},^{Footnote 37}. Multi-drug resistant P. falciparum has been reported in the Greater Mekong subregion^{Footnote 38}.

Susceptibility to disinfectants

Plasmodium spp. are susceptible to quaternary ammonium compounds^{Footnote 39},^{Footnote 40}, ethanol, and sodium hypochlorite^{Footnote 41}.

Physical inactivation

Riboflavin/UV treatment has been used to inactivate Plasmodium parasites in whole blood and blood products^{Footnote 42},^{Footnote 43}. Plasmodium parasites are sensitive to heat^{Footnote 44}; gametocytes are inactivated by heat treatment at 56 °C for 2 hours^{Footnote 45}.

Survival outside host

Plasmodium spp. can survive for at least 14 days in whole blood stored at 4 °C^{Footnote 46},^{Footnote 47}. P. falciparum gametocytes in nutrient medium have a half-life of approximately 2.5 days at 37 °C^{Footnote 48}.

Section V: First aid/medical

Surveillance

Blood film staining with Giemsa is often used in the microscopic identification of Plasmodium spp. that cause human malaria^{Footnote 7},^{Footnote 49},^{Footnote 50}. Density thresholds of P. falciparum in blood have been used to establish whether Plasmodium presence in the blood is responsible for clinical symptoms or if the individual is an asymptomatic carrier of P. falciparum with a non-malarial febrile illness^{Footnote 16}. Parasite density thresholds vary according to age group^{Footnote 16}. Antigen-based detection tests are increasingly being used in malaria diagnosis; however detection limit and species specificity are variable among tests^{Footnote 50}. PCR has also been used to detect P. falciparum in blood samples^{Footnote 50},^{Footnote 51}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

For uncomplicated malaria, artemisinin-based compounds are often paired with longer lasting partner drugs (e.g., amodiaquine, lumefantrine)^{Footnote 36},^{Footnote 52}. Severe malaria is usually treated with artesunate for 24 hours, followed by artemisinin-based combination therapy^{Footnote 25}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

In 2019, the first malaria vaccine (RTS,S/AS01 Mosquirix™ manufactured by GSK) was launched in high malaria transmission regions of Africa^{Footnote 53}. Vaccine efficacy in children 5-17 months given a 4-dose regimen was approximately 36% over a 4-year period^{Footnote 54}. A sporozoite-based vaccine PfSPZ (Sanaria Inc.) is undergoing clinical trials in Africa^{Footnote 2}. No vaccine is currently approved for use in Canada.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

Seasonal chemoprevention for children living in areas with highly seasonal malaria transmission is recommended by the WHO^{Footnote 25},^{Footnote 36}. Programs providing intermittent chemoprophylaxis treatment for pregnant women have been implemented in 12 malaria-endemic countries^{Footnote 25}. Chemoprophylaxis treatment is also recommended for individuals travelling to endemic areas^{Footnote 55}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI: Laboratory hazard

Laboratory-acquired infections

Fifteen laboratory-acquired cases of P. falciparum infection have been reported^{Footnote 56}. Four of these were vector-borne cases involving P. falciparum-infected mosquitos^{Footnote 56}. Four cases involved needlestick injuries^{Footnote 56}. Two cases involved accidents with infectious material on glassware that resulted in puncture wounds^{Footnote 56}. One individual developed a P. falciparum infection after he accidentally punctured his finger while performing an autopsy^{Footnote 56}. The circumstances of the other cases were unknown.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

The primary biological specimen is blood.

Primary hazards

The primary exposure hazards are autoinoculation with infectious material, and working with P. falciparum-infected mosquitos.

Special hazards

None.

Section VII: Exposure controls/personal protection

Risk group classification

P. falciparum is a Risk Group 2 human pathogen and Risk Group 1 animal pathogen^{Footnote 57},^{Footnote 58}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the CBS are to be followed. At minimum, it is recommended to use a lab coat and closed-toes cleanable shoes, gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

For Containment Level 2: A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

The use of needles and syringes is to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes is to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

For diagnostic laboratories handling primary specimens that may contain Plasmodium falciparum, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII: Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials should be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area/third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

Containment Level 2: The applicable Containment Level 2 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone are to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX: Regulatory and other information

Canadian regulatory information

Controlled activities with P. falciparum require a Human Pathogens and Toxins Licence, issued by the Public Health Agency of Canada^{Footnote 57}.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• National Notifiable Disease (human)
• Transportation of Dangerous Goods Regulations

Last file update

November, 2019

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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