Primary prevention
Provision of targeted and appropriately delivered preventive messages and services for travellers should be a priority.[32] Most Anopheles mosquitoes bite in the evening and at night. Therefore, people should be advised to protect themselves from infection by avoiding outdoor activity after sunset, using insect repellents, wearing long-sleeved shirts and trousers, and sleeping under insecticide-treated bed nets.
Chemoprophylaxis for travellers
Non-immune adults and children travelling to endemic or high-risk areas should take antimalarial chemoprophylaxis.[44]
Chemoprophylaxis is not recommended for destinations where malaria cases occur sporadically and the risk for infection to travellers is assessed as being low.
Chemoprophylaxis regimens vary and you should consult your local guidance for more information on choice of regimens.[44]
Choice depends on several factors including the presence of drug resistance in the area of travel, length of travel, patient’s other medical conditions and medications, patient’s allergy history, and potential adverse effects. Long-term travellers (travel >6 months) have additional considerations.
Chloroquine- and mefloquine-resistance is an issue in many parts of the world. Consult your local guidelines for up to date information on drug resistance in specific areas of travel.
The Centers for Disease Control and Prevention (CDC) recommends the following chemoprophylaxis regimens:[44]
atovaquone/proguanil: 1-2 days prior to travel, daily during travel, and for 7 days after leaving the endemic area
doxycycline: 1-2 days prior to travel, daily during travel, and for 4 weeks after leaving the endemic area
chloroquine or hydroxychloroquine: 1-2 weeks prior to travel, weekly (same day each week) during travel, and for 4 weeks after leaving the endemic area
mefloquine: ≥2 weeks prior to travel, weekly (same day each week) during travel, and for 4 weeks after leaving the endemic area
primaquine: 1-2 days prior to travel, daily during travel, and for 7 days after leaving the endemic area
tafenoquine: 3 days prior to travel, weekly (same day each week) during travel, and one additional dose 1 week after leaving the endemic area (recommended for adults only).
Regimens should be catered to the individual and their circumstances. Certain drugs may not be recommended in children, pregnant or breastfeeding women, or people with certain conditions (e.g., psychotic disorders). Consult your local guidance for more information.[44]
Atovaquone/proguanil and doxycycline are useful for last-minute travel as they are started 1-2 days prior to travel and can be used in all malaria-endemic areas. However, they require daily dosing, and some people may prefer to take a drug with weekly dosing.
Chloroquine and hydroxychloroquine should only be used for travel to areas with chloroquine-sensitive malaria.
Primaquine is recommended primarily for short-duration travel to areas with principally P vivax.
Tafenoquine is a good choice for shorter trips and last-minute adult travellers due to its more convenient regimen, and is suitable for both P vivax and P falciparum prevention. However, it is only recommended for adults.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency must be ruled out by appropriate laboratory testing before using primaquine or tafenoquine due to the risk of fatal haemolysis.
Travellers going to Plasmodium ovale-endemic areas should be warned of potential symptoms and signs of malaria. Only those people who have prolonged exposure in high-transmission regions (e.g., western Pacific) should be advised to take post-exposure prophylaxis with primaquine (administered for 14 days after leaving the endemic area).[44]
Travellers going to low-risk Plasmodium vivax areas can travel without chemoprophylaxis. However, travellers to high-risk P vivax areas (e.g., Papua New Guinea, Solomon islands) require both pre- and post-exposure prophylaxis with primaquine.[45] Primaquine is the most effective prophylactic agent for P vivax malaria in non-pregnant patients who do not have G6PD deficiency.[45]
Travellers going to Plasmodium knowlesi-endemic areas (e.g., parts of Southeast Asia) should take the same chemoprophylaxis as for P vivax areas.
Pregnant women should avoid travel to areas with malaria transmission if possible. However, if travel to a malarious area cannot be deferred, use of an effective chemoprophylaxis regimen is essential, along with mosquito avoidance measures.[44] There is increasing evidence for the safety of chemoprophylaxis administered in all stages of pregnancy based on studies of patients who live in endemic areas.[46]
There is good evidence for clinically important benefits on anaemia and parasitaemia in the mother, and on birth weight in infants, with a range of prophylaxis regimens from studies in endemic areas. [
]
The safety of mefloquine in pregnant women is based on case series, randomised controlled trials, and limited pregnancy outcome data, but it shows a similar safety profile to that seen in endemic population studies. One Cochrane review of over 8000 pregnant women found that mefloquine is effective and safe in regards to adverse pregnancy outcomes (including low birth weight, prematurity, abortions, stillbirths, and congenital malformations) compared with prophylaxis with sulfadoxine/pyrimethamine (in HIV-uninfected women) or trimethoprim/sulfamethoxazole (in HIV-infected women), both of which are used for prevention in endemic areas such as Africa. However, mefloquine is associated with an increased risk of adverse effects such as dizziness, vomiting, and fatigue.[47] [
]
[ ]
[Evidence A]
In areas with documented mefloquine resistance, there are no current safe and effective chemoprophylactic agents for pregnant women, as these areas are considered multidrug resistant. In such circumstances, pregnant women are advised not to travel. Doxycycline is considered to be contraindicated in pregnant women by most authorities (although, it can possibly be used as a prophylactic agent during the first 15 weeks of pregnancy if other options are unsuitable). Atovaquone/proguanil is also not recommended in pregnancy, although data on the individual components are reassuring.[48]
Consult a specialist for further guidance on chemoprophylaxis regimens in pregnant women.
Presumptive anti-relapse therapy (use of a medication towards the end of the exposure period, or immediately thereafter, to prevent relapses or delayed-onset clinical presentations of malaria caused by hypnozoites of P vivax or P ovale), may be recommended for people who have had prolonged exposure in endemic areas (e.g., missionaries, military personnel).[44]
Vaccines
The World Health Organization (WHO) recommends the use of malaria vaccines for the prevention of P falciparum malaria in children living in malaria-endemic areas, prioritising areas of moderate and high transmission.[49] Vaccines are not recommended for use in travellers.
There are two vaccines currently available: the RTS,S/AS01 vaccine, and the R21/Matrix-M adjuvant vaccine. These vaccines are recombinant protein virus-like particle vaccines that target the central repeat amino acid sequence region of the P falciparum circumsporozoite protein.
Vaccines are recommended in children aged ≥5 months and are administered as a four-dose schedule. Consult your local immunisation schedule for more information.
The RTS,S/AS01 and R21/Matrix-M vaccines have not been tested in head-to-head trials.[50]
RTS,S/AS01 vaccine
The vaccine has been evaluated in a phase 3 study. During the 4-year study period, in children aged 5-17 months who received the vaccine, efficacy was 39% (against clinical malaria) and 31.5% (against severe malaria). Vaccine efficacy against all-cause hospitalisation was 14.9%. This level of protection would provide a significant reduction in morbidity and mortality if rolled out across malaria-endemic regions.[51] However, concerns have been raised with the study.[52]
A randomised controlled trial found that administration of the RTS,S/AS01 malaria vaccine was non-inferior to annual courses of chemoprevention (with sulfadoxine/pyrimethamine and amodiaquine) in preventing uncomplicated malaria over a period of 3 years, and the combination of these interventions resulted in a lower incidence of uncomplicated malaria, hospital admissions with severe malaria, and death than from either intervention alone.[53]
R21/Matrix-M adjuvant vaccine
A phase 3 double-blind, randomised trial in Africa found high efficacy with a three-dose regimen with both seasonal and perennial vaccine administration regimens (75% and 68%, respectively, for 12-month efficacy). However, the trial was insufficiently powered to show protection against severe malaria.[54]
Plasmodium falciparum sporozoite (PfSPZ) vaccine is a whole malaria sporozoite vaccine that has been reported to be well tolerated, safe, and effective in early-stage trials.[55][56] It has received fast-track designation in the US from the Food and Drug Administration (FDA). Other vaccines are in development, including vaccines for P vivax.[57][58]
Insecticidal nets
The WHO recommends pyrethroid-only, long-lasting insecticidal nets that have been prequalified by WHO for deployment for the prevention and control of malaria in areas with ongoing malaria transmission. Piperonyl butoxide-pyrethroid, pyrethroid-chlorfenapyr, or pyrethroid-pyriproxyfen nets may be used in areas where there is pyrethroid resistance. WHO strongly recommends insecticidal nets in areas with ongoing malaria transmission affected by a humanitarian emergency.[49]
Insecticide-treated bed nets are effective at reducing malaria‐related illness and child mortality in affected areas when compared with no nets or untreated nets, despite the increase in insecticide-resistance frequency.[59] [
]
Dual-treated bed nets (i.e., nets treated with 2 different insecticides) may provide better protection than standard bed nets in areas where resistance is a problem.[60] Piperonyl butoxide-pyrethroid nets are better at killing mosquitoes and preventing them from blood feeding compared with standard pyrethroid-only nets in areas where mosquitoes show high levels of resistance to pyrethroids.[61]
Indoor residual spraying
WHO recommends indoor residual spraying be deployed, using a product prequalified by WHO based on the insecticide susceptibility of the local malaria vector(s), for the prevention and control of malaria in children and adults living in areas with ongoing malaria transmission. WHO conditionally recommends against combining indoor residual spraying with insecticide-treated nets. WHO conditionally recommends indoor residual spraying in areas with ongoing malaria transmission affected by a humanitarian emergency. WHO considers dichlorodiphenyltrichloroethane (DDT) to be a last resort, not a first choice.[49]
In communities using insecticide-treated nets, the addition of indoor residual spraying (the regular application of insecticides to household walls) with a non-pyrethroid-like insecticide was associated with reduced malaria parasite prevalence. On average, the incidence of malaria may also be reduced; however, the effect may not be observed in all settings. Benefits have not been observed with pyrethroid‐like insecticides.[62]
Topical insect repellents
WHO conditionally recommends against the use of topical repellents and insecticide-treated clothing for the prevention and control of malaria at the community level in areas with ongoing malaria transmission. However, insecticide-treated clothing may be beneficial as an intervention to provide personal protection against malaria in specific population groups.[49]
One Cochrane review found insufficient evidence to conclude whether topical repellents prevent malaria in settings where other vector control interventions (e.g., insecticide-treated nets) are in place, based on low-certainty evidence. However, there may be a modest beneficial effect among high-risk populations (specifically refugees) who may not have access to other standard vector control measures.[63] [
]
[ ]
House screening
WHO conditionally recommends the use of untreated screening of residential houses for the prevention and control of malaria in areas with ongoing malaria transmission.[49]
Covering potential house entry points with netting or mesh (screening) may reduce malaria transmission and infection in people living in the house.
One Cochrane review found that house modifications, largely screening and sometimes combined with insecticide and lure-and-kill devices, are associated with a reduction in malaria parasite prevalence and a reduction in people with anaemia. The findings on the incidence of malaria were mixed.[64]
Environmental controls
WHO makes no recommendation on the use of larvivorous fish for the prevention and control of malaria because no evidence on efficacy has been identified.[49]
Fish species that eat mosquito larvae and pupae, such as larvivorous fish, have been used in water collections near where people live (e.g., ponds, rivers) in an attempt to decrease Plasmodium parasite transmission. However, one Cochrane review did not find any reliable evidence to support this prevention method for reducing either the density of mosquito populations or malaria transmission.[65]
WHO conditionally recommends against space spraying for the prevention and control of malaria in areas with ongoing malaria transmission.[49]
Space spraying (i.e., the dispersal of a liquid fog of insecticide in an outdoor area) has been used to kill adult insects in public health control programmes. However, one Cochrane review identified only one study that suggested space spraying led to a decrease in the number of malaria cases. This trial was conducted over 30 years ago and within one state in India; therefore, it is uncertain whether these findings are applicable to other areas.[66]
WHO conditionally recommends larviciding for the prevention and control of malaria in areas with ongoing malaria transmission as a supplementary intervention in areas where optimal coverage with insecticide-treated nets or indoor residual spraying been achieved, where aquatic habitats are few, fixed, and findable, and where its application is both feasible and cost-effective.[49]
Larviciding is the regular application of microbial or chemical insecticides to water bodies or containers to kill aquatic immature forms of the mosquito, with the aim of reducing the number that reach adulthood and therefore reducing malaria transmission.
One Cochrane review found that larviciding for non-extensive larval habitats may have an effect on malaria transmission, but the effect in large-scale habitats is not known.[67]
Perennial malaria chemoprevention (PMC)
WHO recommends PMC (formerly known as intermittent preventive treatment in infants, or IPTi) in children belonging to age groups at high risk of severe disease in areas of moderate to high perennial malaria transmission (i.e., areas with P falciparum parasite prevalence >10% or an annual parasite incidence >250 per 1000). Sulfadoxine/pyrimethamine has been widely used for PMC in Africa. Artemisinin-based combination therapies (ACT) have also been used for PMC, but evidence on their safety and efficacy is limited. PMC schedules should be informed by the age pattern of severe malaria admissions, the duration of protection of the selected drug, and the feasibility and affordability of delivering each additional PMC course.[49]
One Cochrane review found that while PMC probably reduces the risk of clinical malaria, hospital admission, parasitaemia, and anaemia, it has not been shown to reduce all-cause mortality, although fewer than 20,000 children were included in the analysis. Evidence from studies over a 19-year period shows declining efficacy of sulfadoxine/pyrimethamine, likely due to increasing drug resistance.[68]
Seasonal malaria chemoprevention (SMC)
WHO recommends SMC in children belonging to age groups at high risk of severe malaria, during peak malaria transmission seasons. Monthly cycles of sulfadoxine/pyrimethamine plus amodiaquine have been widely used for SMC in African children aged <5 years, and have been shown to be safe, efficacious, and well tolerated.[49]
A systematic review and meta-analysis found that SMC resulted in substantial reductions in malaria incidence and prevalence, as well as moderate reductions in severe malaria and anaemia, among children <5 years of age and ≥5 years of age. In areas of moderate to high transmission, SMC reduced all-cause hospitalisation and moderate anaemia among children <5 years of age; however, no mortality reduction was detected.[69]
Intermittent preventive treatment of malaria in school-aged children (IPTsc)
WHO recommends that school-aged children (i.e., 5-15 years) living in malaria-endemic settings with moderate to high perennial or seasonal transmission should be given a full therapeutic course of an antimalarial drug at predetermined times as chemoprevention. First- and second-line malaria treatments should not be used for IPTsc if safe and effective alternatives are available.[49]
Intermittent preventive treatment of malaria in pregnancy (IPTp)
WHO recommends IPTp with sulfadoxine/pyrimethamine in pregnant women of all gravidities in malaria-endemic areas. IPTp should be started as early as possible in the second trimester of pregnancy, but not before week 13. Doses should be given at least 1 month apart, with the objective of ensuring that at least three doses are given.[49]
Resistance to sulfadoxine/pyrimethamine is increasing; however, ACT has yet to be recommended for IPTp. This is because ACT has not been demonstrated to lead to improved pregnancy outcomes compared with sulfadoxine/pyrimethamine. It is thought that some of the benefits associated with sulfadoxine/pyrimethamine for IPTp may be unrelated to malaria treatment.[49]
Pregnant women with HIV are likely to be on trimethoprim/sulfamethoxazole for the prevention of opportunistic infections associated with HIV, and cannot receive sulfadoxine/pyrimethamine due to drug-drug interactions.
A Cochrane review found that the addition of dihydroartemisinin/piperaquine to trimethoprim/sulfamethoxazole prophylaxis appears to be effective in preventing malaria infection in HIV‐positive pregnant women compared to trimethoprim/sulfamethoxazole alone. However, further research is required.[70]
Post-discharge malaria chemoprevention (PDMC)
WHO recommends that children admitted to hospital with severe anaemia (not due to blood loss following trauma, surgery, malignancy, or a bleeding disorder) who are living in settings with moderate to high malaria transmission should be given a full therapeutic course of an antimalarial drug at predetermined times following discharge from hospital.[49]
Mass drug administration (MDA)
MDA is the administration of a full treatment course of antimalarial medication to every member of a defined population or every person living in a defined geographical area (even asymptomatic people and regardless of whether malaria is present, except those for whom the medication could be harmful) at approximately the same time and often at repeated intervals.
WHO recommends MDA for chemoprevention in areas of moderate to high malaria transmission of P falciparum to provide short-term reductions in disease burden. MDA may be used for burden reduction during emergencies or periods of health service disruption. MDA is recommended in areas with very low to low levels of P falciparum transmission in order to reduce transmission, but it is not recommended in areas with moderate to high levels of P falciparum transmission. MDA is recommended in areas of P vivax transmission in order to reduce transmission to reduce transmission.[49]
A Cochrane review found that MDA did not reduce malaria in the population in areas with a malaria prevalence of ≥10% (moderate to high transmission areas), based on low‐certainty evidence. However, MDA did reduce malaria in the population in areas with malaria prevalence <10% (very low to low transmission areas) immediately after MDA was stopped based on low‐certainty evidence.[71]
Secondary prevention
Most countries require reporting of malaria so that epidemiological data can be collected.
Malaria is not contagious in non-endemic areas, due to the lack of an appropriate mosquito vector. Prophylaxis of close contacts is unnecessary. It should be borne in mind, however, that family members may have travelled with the patient and had the same exposures and may also be developing malaria. Advice should be given to these people to seek medical attention if they develop symptoms.
Appropriate advice regarding future antimalarial prophylaxis should be given to the patient to prevent further episodes. Patients' attitudes about antimalarial prophylaxis will vary depending on their prior experiences and duration of stay in endemic regions.
Use of this content is subject to our disclaimer