Malaria Prevention & Control:

Outbreak Investigation, Occurrence Factors & Control Measures

Introduction

Malaria is a parasitic, protozoal, vector-borne disease that is caused by the parasite Plasmodium falciparum, P. vivax, P. ovale, and P. malariae infecting Anopheles sp. mosquitoes that infect humans via biting. Once bitten, the parasite enters the human bloodstream, causing pathology after the respective incubation period (Table 1) (1–3). Please reference Figure 1 for the malaria life cycle (4).

The parasite can cause pathology, but the immune response to the parasite is more likely to cause symptoms. These symptoms include fever, nausea, headache, and can progress to severe anemia, cerebral malaria, and multi-organ disease. If left untreated malaria can lead to a high fatality rate, with children, pregnant women, the immunosuppressed, and the elderly being particularly at-risk. Humans are the most important reservoir for Plasmodium spp. survival (1–3).

Malaria is completely preventable and curable, but untreated can be fatal (1). Partial immunity can be developed by those living in endemic areas; however, this requires numerous infections (1–3).

According to the WHO, there were 241 million cases and 627,000 deaths in 2020, which is a very high burden of disease, but 1.7 billion cases and 10.6 million deaths were averted from 2000 to 2020. This illustrates that prevention and control are key strategies in the elimination of malaria worldwide (5–7).

Outbreak Investigation

Outbreak investigation with malaria will have many overlapping steps. First, the outbreak or increase in cases needs to be detected. Assuming the number of fevers or malaria cases has gone up, the cases may have already been confirmed by a lab. If it was not determined to be malaria, there would need to be a confirmation done using blood samples. Cases are often detected through passive case detection (PCD) which is a type of surveillance that is done when patients seek care from a health worker (4, 7).

Once the disease has been identified, the investigation continues to look for more people that may be affected, where they may have been affected, and over what period (4). WHO guidelines require that malaria cases be investigated within three days of confirmation (5, 8). Generally, in all outbreaks, a map is drawn where the outbreak occurred and with malaria, this is particularly important due to environmental factors playing such a significant role in transmission (4). Once the location of the vector is located, control measures can begin. Occurrence factors will be explained in detail later but help to determine further control and preventative actions (3).

A hypothesis should be generated based on data. Control methods should be started, continued, and/or changed based on initial findings while the full investigation continues (4). Control methods should evolve as more information is revealed.

Confirmation of malaria is done through the case definition: positive result on one type of test: microscopy, rapid diagnostic, or polymerase chain reaction (PCR). There is also ‘clinically diagnosed malaria’, where patients exude signs and symptoms but have not taken a positive test (5, 8). In endemic or outbreak situations, these clinical cases will be treated under Mass Fever Treatment (MFT) regimens (3).

After confirmation, WHO notification guidelines require that cases of malaria be reported within one day of confirmation (5, 8).

Next, data from each case needs to be collected and analyzed to determine trends within the investigation. For malaria, this information includes age, sex, occupation, addresses, type of disease, date of onset, and confirmation (4–5, 8).

Further, treatment is done at different stages of the malaria life cycle as well as treatment of the symptoms. For instance, blood transfusions for anemia are common. Quinolones such as Chloroquine, Quinine, Lumefantrine, Amodiaquine are used to inhibit Hematin production, killing the parasite. Antibiotics such as sulfonamides are also used to target enzyme production. Primaquine targets infected hepatocytes. MFT includes Artemisinin Combo Therapy (ACT) to kill malaria parasites through lipid damage and also interfere with Hematin production. Atovaquone and Doxycyclin inhibit energy production at the sexual stage of the life cycle and protein synthesis, respectively, and are the last resort due to their side effects. These cannot be used in pregnancy cases. It is important to note that there are many different treatment plans based on the severity of the case as well as age and if the patient is pregnant. Resistance to several of these treatments in every category has been identified and should be taken into consideration when developing a treatment plan (3).

Interruption of transmission and prevention of recurrence is required within seven days of confirmation according to WHO guidelines (5, 8). For malaria, this includes measures specific to the given situation and now includes vaccination of those residing in the same location, well as mass prevention measures such as Mass Screen and Treat (MST), Targeted Mass Drug Administration (TMDA), knock-down sprays, Indoor Residual Spraying (IRS), and mass dispersal of Insecticide Treated Nets/Long-Lasting Insecticidal Nets (ITN/LLINs) (2, 5). Ultimately, stopping transmission from the infected mosquito to the human reservoir is most important, but all interruption methods will also prevent a recurrence.

In tandem with prevention and control, surveillance will help to detect new cases and determine future action. Surveillance is the “continuous and systematic collection, analysis and interpretation of disease-specific data, and the use of that data in the planning, implementation, and evaluation of public health practice” (9). Surveillance objectives are to reduce the burden of malaria and eventually aim to eliminate the disease, preventing any recurrences (5). As transmission decreases, surveillance type needs to evolve because of the epidemiology of the disease changes. As malaria becomes more focal, the intensity and frequency of reporting increases, often becoming near-real-time case data (9). This means going from monthly aggregate reporting in endemic/outbreak areas to immediate notification in a zero-maintaining zone (9). Cases can also be found from active or reactive case detection (ACD, RCD), which is done in vulnerable and high-risk populations, hard-to-reach populations, or low-transmission settings. RCD will be done after detecting a case with either PCD or ACD (7).

After all the data is collected a report should be written analyzing findings, laying out the methods of control and treatment of cases. The report should be published to disseminate learnings and successes as well as areas for future growth and research. The report should be shared with the global community. It should also be noted that the investigation steps from confirmation, reporting, analysis, reporting, and interpretation to dissemination and use of information are a constant cycle (9). This cycle will continue until malaria is eliminated.

Occurrence Factors

Occurrence factors for malaria are numerous and are often associated with a history of endemicity. This can occur where there is high vectorial capacity and is associated with areas of high malarial transmission. Two main factors are environmental and social.

Environmental changes, natural and human, are highly associated with malaria occurrence. Urbanization, development (oil pipelines, dams, mining, etc.), deforestation, infrastructure (water, sanitation, waste collection), and natural disasters are all associated with high occurrences of malaria as it leads to a disruption of vector breeding grounds. Each country will have specific environmental conditions which can lead to increases in malaria transmission and it is important to determine these and help to prevent these conditions. Seasonality is also significant as temperature, humidity, rainfall, soil quality, and elevation are all factors in transmission (7, 10). Climate change is also associated with an increase in cases due to an increase in environmental disruption and should be taken into consideration during outbreak investigation and long-term prevention measures (7).

Social factors are also highly associated with malaria occurrence. They include demographics, culture, behavior, migration patterns, socioeconomic status, and politics. This influences whether the uptake of control and prevention measures are successful. For example, mass migration events are often associated with high rates of transmission, as well as areas of conflict. Behavior is another example, where ITN and LLIN use is the main prevention mechanism across LMIC and therefore modifications of behavior are necessary. This is also important when it comes to water storage and ensuring communities can drain breeding sites. Access to health care is also an important factor as it influences severe disease, death, and control efforts, including access to treatment and control measures that are not vector resistant (7, 10).

Control & Prevention

Figure 2 shows the numerous ways malaria can be controlled and prevented. Several simultaneous methods are the best way to prevent malaria transmission as none of these methods are 100% effective on their own.

Personal prevention methods can be effective methods of prevention when used concurrently with other methods. Chemoprophylaxis cannot be used consistently in endemic areas as they have side effects and several of these drugs have seen vector resistance. These can be used for travelers to endemic areas where resistance has not yet been detected (3, 11). ITNs, especially LLINs are extremely effective at preventing malaria and are used ubiquitously used across LMICs and endemic areas. The insecticide works to kill the mosquito which is attracted to the person underneath it. Vector resistance to some has been detected in certain locations, but new LLINs are being developed and should be disseminated quickly throughout endemic areas (3). Many examples of LLINs are listed in Figure 2 and include one new approach that my team at the Bill & Melinda Gates Foundation is testing alongside the Ifakara Health Institute, IVCC, and LSHTM: Vector Guard. LLINs are extremely effective when used properly. They are cost-effective and can go a long way in helping to prevent malaria when used in tandem with other methods (3). Biting prevention involves using personal clothing, repellents, mosquito coils, window coverings/mesh, and vaporizers to deter or block mosquitos from breaking the skin and therefore preventing transmission. This can be effective in prevention, especially in endemic areas, but should be used alongside other methods.

RTS, S is a brand-new vaccine that has been approved and is now in use. It has been successful in preventing malaria but has only shown moderate efficacy (5, 12). There are about a dozen other malaria vaccine candidates targeted at different stages of the life cycle, but each comes with its challenges including high resistance, plasticity, antigenic variability, and a complex life cycle (13–15). Some of these candidates include pre-erythrocytic vaccines, whole sporozoite vaccines, blood-stage vaccines, novel BSV antigen vaccines, placental malaria vaccines, circumsporozoite protein (CSP) vaccines, transmission-blocking vaccines, P. vivax vaccines, and vaccines using Alum as a potential adjuvant to help improve efficacy (12, 16–19). There is also much research being conducted on how to better the RTS, S vaccine as it has been the most successful candidate so far and it is cost-effective. For now, RTS, S can be used in combination with other prevention measures for higher overall effectiveness.

Vector control has two main goals: to protect people from infective bites and to reduce community transmission (3, 5). Biological control involves bacterial toxins, botanical compounds, and the introduction of predators to control the vector population in a given area via larvicides/insecticides. This is effective, but new adults will continue to be produced and so this needs to be done repetitively (4, 20). Similarly, chemical control compounds will still kill the larvae or insects in a given area. This also includes IRS, which would use DDT to kill insects inside houses. This is not as common anymore due to people not wanting their houses sprayed continuously (3, 5). Growing resistance to these insecticides and larvicides has also been noted (21). Environmental control includes changes to the natural or human environment that help with the occurrence factors explained above. This will include limiting breeding grounds through draining sites, preventing urbanization, deforestation, and climate change. This also includes preventing the storage of water which increases breeding sites for the vector as well (3, 5, 10).

Mass community control measures should be used in the event of outbreaks and include MDA, MSAT, and MFT (2–3, 6, 9). MDA is not as widely used as it once was due to Artemisinin and other drug resistance detection (23). IPTp and IPTi (pregnancy and infancy) can be used in areas of moderate to high transmission and are types of preventative chemotherapy as well as Seasonal Malaria Chemotherapy (SMC) as a method of control (3).

Some novel control strategy examples are listed in Figure 2 and are still being researched and developed regularly and will continue to be so long as resistance, antigenic variability, and plasticity keep increasing (24–26).

A combination of vector control and personal prevention is the most effective way to prevent transmission. In endemic or outbreak areas, these methods can be used with mass community control to get malaria transmission under control.

Outbreak Causes & Recommendations

Potential causes for an increase in cases could be a multitude of intersecting factors, but the most likely ones are an increase In AMR to LLINs or other prevention methods, an increase in environmental disruption from natural disasters or mass migration because of climate change, lack of access to preventative health care, and seasonality increases due to temperature, humidity, rainfall, etc. Advice to the MoH based on these three factors would have both short- and long-term goals (2–3, 7, 11, 27–30).

Short-term, MSAT, MFT, and possible TMDA of the region depending on the intensity of transmission, keeping resistance in mind. Environmental and chemical control methods of breeding grounds as well as spraying the area to temper transmission. Rapid dissemination of new vector control LLINs, using one where resistance has not been detected in the region, supplementing with RTS, S vaccination of the region where the cases have increased. If cases continue to increase using SMC would also be an option (2–3, 6–7, 11, 28, 30).

Long-term, the MoH should work towards increasing access to preventative healthcare and implementing a Primary and Universal Health Care (PHC, UHC) strategy that would allow the country to eliminate malaria, increasing surveillance measures as transmission rates decrease (7, 9). Research on AMR detection as well as prevention is vital to ensuring the future of malaria prevention (3, 6–7, 11). Mitigating climate change will also go a long way towards eliminating malaria, as these events intensify transmission (6–7, 27, 29).

References

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