Malaria infection is a global problem. It is currently present in 91 countries spread over 8 regions in the world (Central and South America, Hispaniola , Africa, the Middle East, the Indian subcontinent, Southeast Asia, and Oceania), and was previously present in North America, Australia and Europe. In sub-Saharan Africa though, it is very much a daily problem. An estimated 90% of all 200 million malaria cases and 91% of all 445 000 malaria deaths occurred in sub-Saharan Africa in 2016 ] (WHO, 2018), a region where malaria infection is usually endemic (infection is frequent year-round). Sub-Saharan Africa is a large region, consisting of 49 countries (UNDP, n.d.), an area slightly larger than that of China, USA, India and Mexico combined (or 2.4 time larger than Europe), and a population of just more than 1 billion people (The World Bank, 2018). Within the region, incidence still varies considerably within and between countries (Ashley, 2018).

The disease is caused by the Plasmodium parasite, transmitted to humans by the bite of a female Anopheles (Greek: anofelis, “useless”) mosquito that needs blood for the development of its eggs  (Sinka, 2010). Roughly 30-40 species of Anopheles commonly transmit malaria, but Anopheles gambiae is by far the most efficient transmitter. It is specifically adapted to the world in and around human habitations, as it almost uniquely feeds of the blood of humans (Shah, 2010). Tropical regions provide the perfect environment for both Anopheles gambiae and plasmodium parasites. The high temperatures and sunlit, shallow temporary bodies of fresh water provide perfect breeding environments for the mosquitos, while the high temperatures and humidity stimulate parasite growth, increasing the chances of transmission during a blood meal (Collins, n.d.). There are different Plasmodium species, the most famous ones notably Plasmodium (P.) falciparum, vivax, ovale and malariae. As P. falciparum is the most common and most deadly one in sub-Saharan Africa, this article will further focus on this species.

Another factor helping this disease thrive in the region, is the low quality of living. Sub-Saharan Africa has a fast-growing economy (The World Bank, 2014), but also has many of the poorest countries in the world (Focus Economics, 2018). The low quality of living is most notable in rural areas, which in sub-Saharan Africa are usually a mix of farmland and agricultural businesses, forest (also known as ‘the bush’), villages and highly populated towns. These areas can stretch for 100s of kilometers. Access to medical care, education and basic needs (electricity, sanitation and water) are limited, making it very difficult for most people to protect themselves and their families against disease, least of all against one that is vector borne, a vector that is very abundant. It is this demographic, that is hardest done by the disease, and are the least likely to receive aid (Bennett, 2017).

Travelers visiting these regions can protect themselves against malaria by taking chemoprophylaxis, the most common being atovaquone-proguanil (better known as Malarone to the frequent traveler) or doxycycline, a commonly used antibiotic (Ashley, 2018). While these prophylactic drugs provide excellent protection against, they are no option for the locals of these endemic regions, due to possible drug toxicity when used during long periods, resistance and cost. For them, the most cost-effective option to prevent infection are long-lasting insecticide treated bednets (LLINs). Female Anopheles mosquitos feed at night when people are asleep. Bednets prevent mosquitos from biting anyone inside them, and are impregnated by pyrethroids, insecticides that kill adult mosquitos (EPA, n.d.). LLINs are usually distributed free of cost by the government, as part of a single mass distribution project, or as supplementary distribution through antenatal clinics and immunization services (Raghavendra, 2017). During the distribution the receivers are usually educated how to use them, and a list of instructions are given along with the bednets. When used properly, LLINs can have the biggest impact in high transmission areas, having said to reduce malaria-related morbidity by 50% and mortality by 20% in children less than 5 years of age (Hambisa, 2018).There seem to be some issues with adherence however. Most users will follow instructions, but the nets have been known to be used for fishing and protecting food and plants (Dhiman, 2014), and people tend to wash the nets too frequently, which reduces their lifespan (Quive, 2015). It also seems that in larger households, older children are not protected because not enough bednets are available. A recent study found that intensive use of bednets pushes mosquitos to become active earlier in the evening before people go to bed[1]. Overall, to improve usage, there needs to be an improvement in communication during distribution, but nets also need to be more readily available to replace ineffective ones. Indoor residual spraying with insecticides is another option, but it is usually highly dependent on the government, and it is costly to roll out everywhere. In both cases, alternative prevention methods are needed urgently, as widespread pyrethroid resistance in anopheles vectors have been reported, which will reduce their effect (Ashley, 2018).

Mosquitos and parasites aren’t picky, so anyone who finds him- or herself in a malaria endemic area, is at risk. But there are a few population groups at considerably higher risk than others of contracting malaria and developing severe disease. These include pregnant women, patients with HIV/AIDS, and children under 5 years of age (WHO, 2018). In the high-transmission areas of the world, children under 5 years of age (including infants who are initially protected by maternal immunity, but this disappears after roughly 3 months) are the most vulnerable group. They have not had the time to form any kind of acquired immunity against the parasite. Repeated exposure over a long period of time can lead to partial immunity, often seen in older children and adults living in endemic regions. Such “semi-immune” persons can still be infected by malaria parasites but may not develop severe disease (CDC, 2010). If they do develop symptoms, these will generally be milder. The immunity requires a constant rate of infections, and it will be lost after the person leaves an endemic area, or in a population with falling transmission (Harvard, 2013).

Once the parasite is transferred to an individual, it typically takes 10-14 days before it has developed enough to cause symptoms in a human. Most people infected will develop uncomplicated malaria, which manifests itself through very non-specific symptoms, including fever, chills, body-aches, headache, cough and diarrhea (Ashley, 2018). In a few cases, mostly children under the age of 5 years, the disease will develop to severe malaria. Severe malaria usually manifests itself as cerebral malaria, metabolic acidosis and anemia, but also be acute lung or kidney injury (WHO, 2014). All cases of malaria can be fatal if not treated properly, but even when treated, severe malaria can be fatal. The case fatality rate of treated cerebral malaria is usually 10-20% and can reach 50% in pregnant women (Ashley, 2018).

The symptoms of uncomplicated malaria can severely weaken the patient, and if not treated, can last months, causing recurring clinical attacks (every 48-72 hours) interspersed with asymptomatic periods. Getting treatment is not always that easy however (Crowell, 2013). Medical help is often far away, and transport is lacking in rural areas. Only an estimated of 56%-69% of children under 5 years with fever are taken for care in sub-Saharan Africa (Bennett, 2017). Parallel to the disease, is the reduced capacity to work. Many people in rural sub-Saharan Africa have laborious jobs, often working in an agricultural or industrial environment, whilst also having a small farm at home. These jobs, as most others, are not well done while feverish and diarrheal. They usually also have large families to take care of, and sick children need to be taken to a health center, which also results in work time lost. The Ugandan Ministry of Health estimated that 15% of health-related absenteeism from school was due to malaria (Ministry of Health Uganada, 2001). Those lucky enough to work for a company that pays for sick leave won’t lose too much, but in most cases, going to the clinic is a day without pay, and high spending, which results in a high economic burden, especially for the poorest (Hailu, 2017).

The global economy of malaria endemic countries is severely struck by the disease. The 2011 Roll Back Malaria Report indicated that 72% of businesses in sub-Saharan Africa reported a negative malaria impact, with 39% perceiving these impacts to be serious (Novignon, 2016). Good case examples can be found in large agro-industrial (plantation) companies based in rural areas. Due to the remote location, workers and their families are housed on the plantations. The environment created is perfect for mosquitos. Agriculture companies usually need ‘warm and wet’ regions, while the population sizes are sufficient for feeding. One agro-industrial company (Okomu PLC, oil palm and rubber) in Nigeria, reported 8 483 new cases of malaria in 1 year for people registered to the company (employees, contractors, dependents). 6 462 of the cases were diagnosed among the 3 451 large workforce, suggesting there is a yearly incidence rate of 187 cases of malaria per 100 workers. Thankfully many of these companies provide health coverage, including easy drug access and allowing the workers to take time to recover, which is not the case for many people working for smaller businesses or independently. Companies in endemic malaria regions know all to well that the health of the company relies very much on the health of its employees, and that investing in malaria prevention and treatment is essential. A study carried out in Ghana reported that the businesses in their sample spent an average of 0.8% of their corporate budget on malaria prevention and treatment, with an additional 0.5% on other health related corporate social responsibilities (Novignon, 2016). These investments have not gone unnoticed. In recent years increased efforts have been made to close the gap between aid organizations and the private sector, as it is in both party’s best interest to work together.

Global initiatives over the past 2 decades, such as ‘Roll Back Malaria’, ‘President’s Malaria Initiative’ and the ‘MDGs’ and ‘SDGs’ increased accessibility to quality malaria treatment and diagnostic tools, and lowered costs (WHO, 2017), but it is still far from good enough. In 2015 it was estimated that 80% of children with malaria did not receive treatment. Much of this is due to poor access to government health centers for patients, but also because often essential drugs are not reaching rural areas, in contrast to urban areas (Bennett, 2017). Supply chains are often hampered by logistical and political issues, leading to stock outs for both diagnostic tools and treatment, which could mean the long trip to the clinic was in vain.

In 2012 the WHO started the ‘T3: Test, Treat, Track initiative’. The first T was being overlooked too often. Since malaria is usually the most common reason to visit the clinic in endemic regions, medical staff would diagnose clinically. This is the fastest way of diagnosing, but also the least specific. Due to non-specific symptoms of malaria, there is a tendency to over-diagnose malaria using this technique, which can harm the patient, wastes medication meant for others, and increases the risk for resistance (Tangpukdee, 2009). Diagnosis should preferably be done by light microscopy. Small amounts of blood are retrieved by pricking the finger of the patient and staining it on a slide. This allows the laboratory staff to identify which species of plasmodium infected the patient, if any, and the parasitemia, which is needed to follow up the effect of treatment. When done correctly, it is the most specific method of diagnosis. It is however a time-consuming procedure (both for staff and patient) and requires trained microscopists, who are not abundantly present (Uzochukwu, 2009). Rapid diagnostic tests (RDTs) have addressed these 2 issues. After a finger prick, a blood drop is administered to the RDT, and 20 minutes later a result is given. The tool is also very easy to use after only a short training. But it does have its own flaws though. Too often there are design and production limitations, which are not picked up by quality assurance. This leads to RDTs not being readable, or to misdiagnosis (Maltha, 2013). Very high falciparum parasitemias can also produce negative results, while parasitemias <1 parasite per µl cannot be detected, which could be essential in regions where eliminating the disease is possible (Ashley, 2018).

The roll out of RDTs has helped for the patient. When used correctly, it has saved ill people many hours awaiting results, or being misdiagnosed by clinical examination. It has also helped get the diagnostic tools closer to them, as community health workers can use the tests anywhere they go.

Once diagnosed, treatment should start immediately. Generally, the recommended treatment for P. falciparum infection is artemisinin-based combination treatments (ACTs). ACTs are a group of drugs that combine artemisinin with another drug (lumefantrine, amodiaquine, piperaquine, mefloquine). Artemisinin is a drug isolated from the plant Artemisia annua, a herb commonly used in Chinese traditional medicine. The co-formulation reduces the possibility of resistance developing against the treatment, as P. falciparum did with chloroquine and antifols (Ashley, 2018). However, resistance to ACT is already present in south-East Asia (WHO, 2017). Artemisinin was found to be a great drug against malaria in China in the 1970s. After this discovery, it was widely used as a monotherapy in Asia. Alternatives to the currently available drug formulations of artemisinin (oral tablets, injection) are sometimes proposed; however due to the lack of well-conducted controlled clinical trials, these alternative formulations can currently not be recommended (Räth, 2004) (Kooy, 2013) (Lagarce, 2016)(Ref)(Ref)(Ref)(Ref). In addition, to make things even more complicated, the use of one single drug to combat malaria makes it much easier for the organism to adapt (Lin, 2010). Fears are large that the resistance could spread to Africa. The higher presence of P. falciparum in Africa could result in substantial increases in morbidity and associated mortality, mainly among children under 5 years of age (Slater, 2016).

The future of new therapies to fight malaria seems quite bleak however. New molecules that can kill the parasites or stop them from reproducing are urgently needed before the resistance to current therapies spreads (Raphemot, 2016). Since 2015, the only malaria vaccine brought to the market, RTS,S/AS01 (Mosquirix®), has been approved.  Due to the overall modest level of protection in infants and young children, resp., the WHO required more studies to be done in Africa, before a wide roll-out can be granted (WHO, 2016).

Much has been done in recent years to reduce the burden that malaria has on sub-Saharan Africans, but much more still needs to be done. Accessibility to prevention tools and treatment need to further improve, and so must basic education about the disease. Every child growing up must know what it can/must do to protect him/herself against this illness and be able to do this easily. Besides that, governments must act stricter on implementing good guidelines on drug use, as a widespread resistance to ACTs would be catastrophic.

References

Ashley, E. A. (2018). Malaria. The Lancet.

Bennett, A. (2017). Population coverage of artemisinin-based combination treatment in children younger than 5 years with fever and Plasmodium falciparum infection in Africa, 2003-2015: a modelling study using data from national surveys. Lancet Glob Health.

CDC. (2010, February 8). https://www.cdc.gov/malaria. Retrieved from https://www.cdc.gov/: https://www.cdc.gov/malaria/about/biology/human_factors.html

Collins, F. (n.d.). https://www.vectorbase.org/organisms/anopheles-gambiae. Retrieved from https://www.vectorbase.org: https://www.vectorbase.org/organisms/anopheles-gambiae

Crowell, V. (2013). A Novel Approach for Measuring the Burden of Uncomplicated Plasmodium falciparum Malaria. PLoS ONE.

Dhiman, S. (2014). Culminating anti-malaria efforts at long lasting insecticidal net? Journal of Infection and Public Health.

EPA. (n.d.). https://www.epa.gov/mosquitocontrol/. Retrieved from https://www.epa.gov: https://www.epa.gov/mosquitocontrol/permethrin-resmethrin-d-phenothrin-sumithrinr-synthetic-pyrethroids-mosquito-control

Focus Economics. (2018, March 7). https://www.focus-economics.com/blog. Retrieved from https://www.focus-economics.com: https://www.focus-economics.com/blog/the-poorest-countries-in-the-world

Hailu, A. (2017). Economic burden of malaria and predictors of cost variability to rural households in south-central Ethiopia. PLoS ONE.

Hambisa, M. T. (2018). Long lasting insecticidal net use and its associated factors in Limmu Seka District, South West Ethiopia. BMC Public Health, 7.

Harvard. (2013, January). https://www.health.harvard.edu/diseases-and-conditions/malaria. Retrieved from https://www.health.harvard.edu: https://www.health.harvard.edu/diseases-and-conditions/malaria

Lin, J. T. (2010). Drug-Resistant Malaria: The Era of ACT. Curr Infect Dis Rep.

Maltha, J. (2013). Malaria rapid diagnostic tests in endemic settings. Clinical Microbiology and Infection.

Nonvignon, J. (2016). Economic burden of malaria on businesses in Ghana: a case for private sector investment in malaria control. Malaria Journal.

Novignon, J. (2016). Economic burden of malaria on businesses in Ghana: a case for private sector investment in malaria control. Malaria Journal.

O’Meara, W. (2009). The impact of primary health care on malaria morbidity – defining access by disease burden. Trop Med Int Health.

Quive, I. M. (2015). Household survey of availability of long-lasting insecticide-treated nets and its determinants in rural Mozambique. Malaria Journal.

Raghavendra, K. (2017). Monitoring of long-lasting insecticidal nets (LLINs) coverage versus utilization: a community-based survey in malaria endemic villages of Central India. Malaria Journal, 8.

Raphemot, R. (2016). Current therapies and future possibilities for drug development against liver-stage malaria. J Clin Invest.

Shah, S. (2010). The Fever: how malaria has ruled humankind for 500,00 years. Picador.

Sinka, M. E. (2010). The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic précis. Parasites & Vectors.

Slater, H. C. (2016). Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa. Malaria Journal.

Tangpukdee, N. (2009). Malaria Diagnosis: A Brief Review. The Korean Journal of Parasitology.

The World Bank. (2014, April 7). http://www.worldbank.org/en/news/press-release. Retrieved from www.worldbank.org: http://www.worldbank.org/en/news/press-release/2014/04/07/africas-growth-set-to-reach-52-percent-in-2014-with-strong-investment-growth-and-household-spending

The World Bank. (2018). https://data.worldbank.org/region/sub-saharan-africa. Retrieved from https://data.worldbank.org: https://data.worldbank.org/region/sub-saharan-africa

Uganda, M. o. (2001). The burden of malaria in Uganda: why all should join hands in the fight against malaria. Ministry of Health Uganda.

UNDP. (n.d.). http://www.africa.undp.org/content/rba/en/home/regioninfo.html. Retrieved from http://www.africa.undp.org: http://www.africa.undp.org/content/rba/en/home/regioninfo.html

Uzochukwu, B. (2009). Cost-effectiveness analysis of rapid diagnostic test, microscopy and syndromic approach in the diagnosis of malaria in Nigeria: implications for scaling-up deployment of ACT. Malaria Journal.

WHO. (2014). Severe Malaria. In WHO, Tropical Medicine and International Health (pp. 7-131). Geneva: The World Health Organization.

WHO. (2017). Artemisinin and artemisinin-based combination therapy resistance.

WHO. (2017). World Malaria Report.

WHO. (2018). http://www.who.int/malaria/. Retrieved from http://www.who.int/: http://www.who.int/malaria/areas/high_risk_groups/en/

[1] Thomsen et al. Mosquito Behavior Change After Distribution of Bednets.  Results in Decreased Protection Against Malaria Exposure.  J Infect Dis 2017;215:790-7.

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