Malaria is an ancient parasitic infection — dating back to 2700 BC — that is transmitted via only female mosquitos of the genus Anopheles. It is the most common disease in Africa and some countries in Asia, occurring primarily in underdeveloped areas. There are 5 species that can infect humans, including Plasmodium malariae, P falciparum, P vivax, P ovale, and P knowlesi.1
In the United States, approximately 2000 patients are diagnosed with malaria each year. The majority of these diagnoses occur during travel to malaria-endemic regions.2 Four autochthonous malaria outbreaks have occurred since 2000. In June 2023, the Centers for Disease Control and Prevention (CDC) identified a total of 7 cases of locally-acquired P vivax malaria in Florida and Texas.4
How Malaria Infections Occur
Nirbhay Kumar, PhD, is a professor in the Department of Global Health at the George Washington University Milken Institute School of Public Health. An expert in the immunobiology of malaria transmission, Dr Kumar has led several international research projects on the immunology of malaria, including preclinical evaluations of vaccines and coinfections with other tropical parasites.
He explained that the significance of this outbreak is its local transmission: “somebody came from abroad who was infected with malaria parasites and locally prevalent Anopheles female mosquitos picked up those parasites and bit more people to transmit those parasites in the community.”
There are 2 phases of malaria infection — asexual and sexual. The sexual phase occurs in mosquitos and the asexual phase occurs in the human host. Once bitten by a carrier mosquito, the malaria sporozoites enter the blood and reach hepatocytes within 30 minutes. The parasites develop in the liver and then later infect the blood, causing rupturing of erythrocytes and subsequent anemia or death.1 The initial presentation of malaria involves cold and flu-like symptoms, including fever, headache, myalgia, diarrhea, shortness of breath, and confusion. For P vivax, a severe infection can cause anemia, jaundice, respiratory distress, impaired consciousness, kidney failure, and death.2
Diagnostic Testing Methods
The gold standard for malaria diagnosis is blood microscopy.1 However, this method requires experienced and properly-trained microscopists to identify the malaria parasites.
“Microscopy is the gold standard, but it requires a lot of training because you are looking for a needle in the haystack. You could have just a very few parasites in the whole blood smear,” Dr Kumar noted.
Blood smears may contain other confounding cells, making it difficult for untrained microscopists to identify the parasites. Although rapid diagnostic testing requires minimal training and can be used to identify a positive infection and differentiate a few species, it is considered complementary to microscopy. Abbott Laboratories’ BinaxNOW malaria test is the only Food and Drug Administration (FDA)-approved rapid testing method that can detect a positive infection. However, it can only differentiate P falciparum and cannot distinguish between P vivax, P ovale, and P malariae.2 It is pertinent for primary care providers (PCPs) to consider rapid diagnostic testing when screening patients for malaria infection.
Advantages and Disadvantages of Direct Diagnostic Testing Methods2
|Type of Direct Diagnostic Test||Species Differentiated||Advantages||Disadvantages|
|Microscopy||All||Fast and cost-effective||Requires proper equipment, training, and experience|
|BinaxNOW Malaria||P Falciparum||Fast and simple||Low sensitivity and accuracy; high cost|
|Polymerase chain reaction||All||Correct diagnosis of type; high sensitivity and accuracy||Long-term high-volume use associated with high cost|
The Challenges of Differential Diagnosis
There are challenges in the differential diagnosis of malaria because malaria is uncommon in the US and shares symptoms with many other infections. For PCPs, it is recommended to take a cautious approach and promptly order diagnostic testing when screening patients for malaria infection, regardless of an individual patient’s travel history.5 It is indispensable for PCPs to spread awareness of the current outbreak, particularly those in close proximity to its epicenter.
According to Dr Kumar, “if patients suffer from symptoms such as fever and chills, do not assume this is just a viral infection because malaria is a lethal infection and can cause death without any warning.”
Obinna Nnedu, MD, MPH, FIDSA, CTropmed, is Director of the Infectious Disease Fellowship program and a board-certified infectious disease specialist with expertise in tropical and travel medicine.
“Malaria usually presents with fever; other symptoms may include body aches, headaches, and shortness of breath,” Dr Nnedu noted. “Unfortunately,” he added, “there are many other diseases that may have similar symptoms.”
Special Populations to Consider for Malaria Management
Following malaria diagnosis, pharmacologic therapy should be initiated immediately. This is critical for individuals diagnosed during pregnancy because the infection may cause fetal loss, low birthweight, or congenital infection.2 Atovaquone-proguanil and tetracycline is contraindicated for pregnant and/or breastfeeding women. Combination therapy with quinine plus clindamycin for 7 days is recommended for the treatment of uncomplicated chloroquine-resistant malaria in pregnancy; artemisinin-based combination therapy can be used in the second and third trimester. Intravenous artesunate is first-line therapy for severe malaria infection during pregnancy, with administration recommended in all trimesters.2
Key Patient Counseling Points
Both Texas and Florida released a statewide health advisory for the public and PCPs following the outbreak. The Florida Department of Health urges the public to be diligent in protecting themselves from mosquitos and adhere to “Drain and Cover” recommendations.6 The public is advised to to drain standing water to stop mosquitoes from multiplying and entering the home, and to cover the skin to protect against mosquito bites.
The Texas Department of State Health Services announced similar recommendations, as follows:7
- Drain water from any receptible in which it can be collected (eg, garbage cans, flowerpots, bottles, cans, appliances, etc);
- Cover doors with screens to keep mosquitoes out of the home;
- Wear shoes, socks, long pants, and long sleeves to protect against bites; and
- Apply mosquito repellent that contains DEET, picaridin, lemon eucalyptus oil, para-menthane-diol, 2-undecanone, and IR3535®.
Dr Nnedu recommends that patients “use mosquito repellant that contains 20% DEET.” “If sunscreen is also being used, apply sunscreen first and then mosquito repellant; the mosquito repellant is effective for 6 hours,” Dr Nnedu noted, adding “Increased perspiration will decrease the amount of time the mosquito repellant is effective.”
Key Recommendations for Clinicians
- Obtain travel history from patients with symptoms suggestive of malaria infection.
- Report incidences of symptomatic malaria infection to local and state health departments.
- Identify the specific malaria species as P vivax and P ovale may remain dormant in the liver and result in chronic infection recurrence after months or years.5
- Encourage fellow clinicians to revisit malaria therapy guidelines and take a continued medical education course on malaria, especially those who practice in Texas and Florida.
- Contact the CDC for guidance on Malaria diagnosis and management.5
According to Dr Nnedu, “Physicians in the affected and surrounding counties [should] screen patients with fever for malaria. The CDC will continue to work with local health departments to keep us informed on malaria risk.”
1. Talapko J, Škrlec I, Alebić T, Jukić M, Včev A. Malaria: the past and the present. Microorganisms. Published online June 21, 2019. doi:10.3390/microorganisms7060179
2. Daily JP, Minuti A, Khan N. Diagnosis, treatment, and prevention of malaria in the us: a review. JAMA. Published online August 2, 2022. doi:10.1001/jama.2022.12366
3. Dye-Braumuller KC, Kanyangarara M. Malaria in the USA: how vulnerable are we to future outbreaks?. Curr Trop Med Rep. Published online January 14, 2021. doi:10.1007/s40475-020-00224-z
4. Locally acquired cases of malaria in Florida and Texas. Centers for Disease Control and Prevention. Updated July 7, 2023. https://www.cdc.gov/malaria/new_info/2023/malaria_florida.html
5. Locally acquired malaria cases identified in the United States. Centers for Disease Control and Prevention. Published online June 26, 2023. https://emergency.cdc.gov/han/2023/han00494.asp
6. The Florida department of health issues mosquito-borne illnesses advisory. Florida Health. Published online June 26, 2023. https://www.floridahealth.gov/diseases-and-conditions/mosquito-borne-diseases/_documents/advisory-statewide-6-26-2023.pdf
7. Health advisory: locally acquired malaria case. Texas Department of State Health Services. Published online June 23, 2023. https://www.dshs.texas.gov/news-alerts/health-advisory-locally-acquired-malaria-case