Malaria is a serious infection and prevention traditionally relies on chemoprophylaxis during and after exposure. The risk of side effects from chemoprophylaxis needs to be balanced against the risk of infection and there has been conducted only one prospective, double-blind study comparing the suspected side effects of mefloquine, atovaquone/proguanil, doxycycline and chloroquine/proguanil. Therefore, the current recommendations are based on descriptive studies and case reports. There is a lack of data on the risk of infection in travelers and the national statistics on the number of imported cases are not very useful as long as the total number of travelers at risk is not known. The risk to travelers is therefore estimated from data on malaria in the indigenous population, while the risk for travelers is expected to be lower. Atovaquone/proguanil has been registered in Europe for travels of up to four weeks, but in the United States there is no upper limit for the duration of use. It is not possible to prescribe efficient prophylaxis to pregnant women in the first trimester or infants below 11 kilograms of body weight travelling to tropical Africa [1].

Chemoprophylaxis In Special Population

Intermittent Preventive Therapy in Pregnancy

For pregnant women who reside in malaria endemic regions, Intermittent Preventive Therapy During Pregnancy (IPTp) with Sulphadoxine/Pyrimethamine (SP) at scheduled antenatal care visits can reduce maternal and neonatal morbidity and mortality. Each dose suppresses or clears any existing asymptomatic infections from the placenta and provides up to 6 weeks of post-treatment prophylaxis. Three doses of IPTp during the second and third trimesters of pregnancy are superior to two doses of IPTp [2].

Intermittent Preventive Therapy in Children

Intermittent Preventive Therapy in Children (IPTC) is an approach used in areas of seasonal malaria transmission, where the primary burden is in older children rather than infants. IPT is administered several times, typically monthly, during the seasonal occurrence of malaria.

Intermittent preventive therapy in infants

In a review of data from six double-blind, randomized, placebo-controlled trials that assessed the efficacy of IPTi was found to have a protective efficacy of 30.3 per cent against clinical malaria, 21.3 per cent against the risk of anaemia, 38.1 per cent against hospital admissions associated with malaria parasitaemia and 22.9 per cent against all-cause hospital admissions. No difference in mortality was demonstrated [3].

Prevention Of Malaria in the Traveler

Fever in the returned traveller should be considered malaria until proven otherwise. Approximately one in three returned international travelers presenting to a specialized travel or tropical medicine clinic, with a systemic febrile illness, has malaria. Prevention of malaria in the traveler can be accomplished via personal protective measures for mosquito bite prevention and the compliant use of an effective antimalarial chemoprophylactic agent. Most travelers who develop malaria do so because they do not adhere to an effective chemoprophylactic drug regimen; however, travelers who do adhere to an effective drug regimen can still develop malaria. Fatalities may be a result of delay in seeking medical treatment, failure to obtain an adequate travel history, delayed diagnosis, laboratory error, late initiation of treatment, and/or inappropriate therapy. 

Selection of an effective chemoprophylactic drug regimen is based on assessment of malaria risk based on an individual’s travel itinerary and resistance patterns and based on the individual’s medical history and preferences. The agents most commonly used for chemoprophylaxis are atovaquone/proguanil, mefloquine, doxycycline and chloroquine. These agents are effective against the erythrocytic stages of the parasite life cycle. 

For travelers to P. vivax and P. ovale endemic regions, terminal prophylaxis with primaquine directed against the liver hypnozoites should be considered at the end of travel. Primaquine can cause severe or fatal haemolysis in individuals with G6PD deficiency. G6PD deficiency must be ruled out with laboratory testing prior to administration [4].

Challenges To Malaria Prevention and Control

Inadequate Surveillance

Current malaria surveillance activities are woefully deficient. Effective surveillance and accurate data are essential to efforts to reduce the burden of malaria. Successful targeting of interventions and pursuit of reasonable strategies for control of malaria are not possible without a clear understanding of the prevalence and incidence of malaria and where it is occurring. Importantly, surveillance also provides information that enables an evaluation of the effectiveness of ongoing interventions and enables redirecting of resources. For these reasons, strong commitments to better data and significant improvements in surveillance systems should be a priority.

Funding

Ultimately sufficient financial support may be the most import- ant factor in the success of lasting reductions of the burden of malaria. Resource constraints have been blamed as the primary reason for the failure of the previous major mobilization against malaria [5]. Adequate funding is also key to capacity development. However, competing priorities at the global and national levels threaten continued allocation of funds. Ultimately, static funding, while admittedly considerable, may not be sufficient to realize permanent decreases in the burden of malaria.

Operational Challenges

It is suggested that the previous global effort to eradicate malaria failed, in part, as a result of requiring scientists to become field managers. Even the best tools and the most noble of goals will be destined to fail without effective implementation. Such implementation requires strong and sustained operational direction and long-term commitments with integration into national health infrastructure and participation of communities [6].

Insecticide Resistance

Sixty-four malaria-endemic countries are currently reporting mosquito resistance to at least one insecticide used for malaria control including pyrethroids. In addition, selective pressure, induced by insecticides, has resulted in modified vector behaviour and emergence of new vectors being observed [7]. 

Repurposing insecticides currently used for agriculture and reformulating current preparations may offer tools to combat vector resistance. Using combinations of insecticides, rotating different preparations and mosaic application are additional approaches to resistance management.

Drug Resistance

Given the existing widespread resistance of P. falciparum to chloroquine and SP, the availability of highly effective artemisinin-based compounds has provided a major tool for reducing the burden of malaria. Subsidies for artemisinin-based combination therapy have led to increased availability and reduced costs. However, reports of emerging artemisinin resistance are cause for concern. Resistance is driven by poor quality and counterfeit medication as well as the use of artemisinin mono- therapy. A recent published report indicates that up to 36 per cent of antimalarial drugs collected in southeast Asia were falsified, whereas in sub-Saharan Africa, a third failed chemical assay analysis [8].

Resistance to SP also threatens to compromise its use for intermittent preventive therapy in pregnancy and for children and infants. Combination therapy using azithromycin and chloroquine may offer an alternative that can provide protection against sexually transmitted infections as well. 

Testing of currently available drugs for antimalarial activity is one of the key approaches to combating drug resistance and can accelerate production of new therapies as well as reduce costs. Itraconazole, posaconazole and atorvastatin are among such commercially available drugs that have demonstrated activity against malaria. In addition, chemical modification of available antimalarials and hybridization of existing drugs to improve their effectiveness and high-throughput screening and molecular modelling are being employed in attempts to identify new potentially effective therapies.

1. J.E. Petersen "Malaria chemoprophylaxis." Ugeskr. Laeger, vol. 167, no. 42, 2005, pp. 3984–3987.

2. K. Kayentao et al. "Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa systematic review and meta-analysis." JAMA, vol. 309, no. –, 2013, pp. 594–604.

3. J.J. Aponte et al."Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants a pooled analysis of six randomised placebo-controlled trials."Lancet, vol. 374, no. –, 2009, pp. 1533–1542.

4. M.E. Wilson et al."Fever in returned travelers results from the GeoSentinel Surveillance Network." Clin. Infect. Dis., vol. 44, no. –, 2007, pp. 1560–1568.

5. J.M. Cohen et al."Malaria resurgence a systematic review and assessment of its causes." Malar. J., vol. 11, no. –, 2012, p. 122.

6. “MALERA Consultative group on monitoring evaluation and surveillance”. A research agenda for malaria eradication monitoring evaluation and surveillance. PLoS Med., vol. 8, no. 1, 2011, e1000400.

7. A. Asidi et al. "Loss of household protection from use of insecticide-treated nets against pyrethroid-resistant mosquitoes Benin." Emerg. Infect. Dis., vol. 18, no. –, 2012, pp. 1101–1106.

8. G.M. Nayyar et al. "Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa." Lancet Infect. Dis., vol. 12, no. –, 2012, pp. 488–496.