Barriers to Timely Diagnosis and Treatment of Vector-Borne Diseases in a Changing Climate: A Case Report

Abstract

This case study examined current trends in the prevalence of vector-borne diseases and the impact of climate change on disease distribution. Our findings indicate that the dynamics of the Anopheles mosquito population in particular has changed dramatically in the past decade and now poses an increasing threat to human populations previously at low risk for malaria transmission. Given their geographic location and propensity for sustaining vector-borne disease outbreaks, southeastern states are particularly vulnerable to climate-induced changes in vector populations. We demonstrate the need to strengthen our hospital and laboratory infrastructure prior to further increases in the incidence of vector-borne diseases by discussing a case of uncomplicated malaria in a patient who arrived in one of our hospitals in Louisiana. This case exemplifies a delay in diagnosis and obtaining appropriate treatment in a timely manner, which suggests that our current health care infrastructure, especially in areas heavily affected by climate change, may not be adequately prepared to protect patients from vector-borne diseases. We conclude our discussion by examining current laboratory protocols in place with suggestions for future actions to combat this increasing threat to public health in the United States.

Health care providers today face many new challenges as our health care policies and the dynamics of patient populations continue to change. While much of the rise or reemergence of certain diseases can be attributed to antibiotic overuse or the increase in international travelers from endemic areas, one aspect that is often overlooked is the impact of climate change on human health. The global mean temperature is currently increasing at a rate of 0.2 °C per decade owing to past and continued carbon emissions. ¹ Warmer air holds more moisture than cooler air does, causing changes in rainfall patterns and soil moisture. ² Because many insect vectors thrive in warm and wet conditions, climate change encourages their survival and can introduce them to previously unfavorable environments, thereby increasing disease incidences and the health care burden to communities that are particularly sensitive to global temperature changes, such as the southeastern United States.

Population expansion of several insect vectors has been documented in the United States. Aedes spp mosquito populations, for example, have substantially increased in distribution in the past decade. This ecological change poses a risk to human health, as Aedes aegypti and Aedes albopictus are the most commonly identified vectors for several mosquito-borne diseases, including Zika, dengue, yellow fever, and chikungunya. These mosquito species thrive primarily in tropical and subtropical climates but are often found in more temperate areas. Both species feed on humans and thereby can easily transmit mosquito-borne diseases, particularly in densely populated regions. ³

A longitudinal study monitoring distribution changes in California found a substantial expansion of A aegypti and A albopictus populations near Los Angeles. From 2011 to 2015, both Aedes spp populations moved from urban coastal to urban central counties despite aggressive control efforts implemented by the state of California. ⁴ Another model predicts the environmental conditions conducive to A albopictus survival will increase by 43% to 49% in the northeastern United States, increasing the probability of disease transmission in warmer and more temperate climates. ⁵

Because of a favorable climate, the southeastern states have historically been at highest risk for local Aedes-borne disease transmission. In 1905, New Orleans was the site of a major yellow fever outbreak. ⁶ In 2013, dengue virus spread locally in Texas, and in 2014, a local outbreak of chikungunya virus was documented in Florida.^7,8 More recently, from 2015 to 2017, the southeastern states were a hotspot for autochthonous transmission of Zika virus. ⁹ With recent changes in Aedes spp mosquito distributions resulting from an increasing global temperature, the threat of local transmission of viruses such as dengue, Zika, chikungunya, and yellow fever has substantially increased in recent years and therefore has implications for public health in the United States.

The vector for malaria, the Anopheles mosquito, is also expected to increase in distribution in the United States based on observations of global expansion patterns. For example, malaria cases have spread into highland regions of East Africa where this disease was not previously endemic, because of unusually warm and wet climates allowing for Anopheles survival and propagation.^10,11 If global temperatures increase by 2 °C to 3 °C, the population at risk for malaria is estimated to increase by 3% to 5%, putting millions of additional people at risk for infection with malaria each year. ¹⁰ In the United States, the number of malaria cases has steadily increased in recent years. A total of 2078 confirmed malaria cases were reported in 2016, a 36.4% increase from 2015. Since then, approximately 2000 cases of malaria are reported each year. ¹² Although most of these cases originated from endemic countries, 156 cases from autochthonous transmission were reported between 1957 and 2003. ¹³ The most recent documented outbreak of locally transmitted malaria occurred in 2003 in Florida, where a total of 8 cases were identified. ¹⁴ Since 2003, no autochthonous outbreaks have been recorded in the United States. Well-established Anopheles mosquito populations exist in multiple states across the country, especially in the northeastern and southern states, where malaria was previously endemic prior to major elimination efforts in the 1950s. ¹⁵

These reports reflect a serious potential for emergence and reemergence of locally transmitted mosquito-borne disease in our nation, especially as climate changes render many regions even more conducive to Aedes and Anopheles survival and disease transmission. Our health care system must be prepared for these major implications of a rapidly changing climate on population health. Although emphasis on primary and secondary prevention measures to eliminate vector-borne infectious diseases is of utmost importance, developing strategies to promptly diagnose and care for a growing patient population also requires immediate attention. We report a case of malaria occurring at University Medical Center in New Orleans and discuss our experience along with other health care provider reports to highlight that current treatment protocols may not be sufficient to meet today’s growing challenges. The patient provided both written and verbal consent for his case to be submitted as a case report. Verbal consent was recorded with permission from the patient during follow-up.

Case Narrative

In July 2017, a 22-year-old male cruise ship worker presented to the emergency department at University Medical Center in New Orleans with headaches, fevers, chills, arthralgias, and myalgias for 4-5 days. He had noticed a cyclical pattern to the severity of his symptoms. Every 2 days, the patient’s symptoms would worsen for at least 24 hours, followed by a period of symptomatic improvement. On the day prior to presentation and admission to the hospital, a physician aboard his cruise ship had made a presumptive diagnosis of malaria. The patient, originally from the New Delhi region of India, had left his home to begin working on the ship as a galley steward less than 2 months prior to having symptoms. The ship had most recently docked in Cozumel, Mexico, and Grand Cayman in the weeks prior to presentation.

Upon admission, the patient received a positive test result on his rapid malaria antigen test. Rapid diagnostic tests (RDTs), which detect antigens derived from the Plasmodium parasite, are advantageous to clinicians because they provide a rapid diagnosis of malaria. RDTs test for antigens that are present in several Plasmodium species, thereby limiting species identification.^16,17 The Plasmodium species is best determined by molecular diagnostic methods such as polymerase chain reaction, which is highly sensitive but costly and time intensive. The use of an RDT does not eliminate the need for confirmatory testing with microscopy. Microscopy, which uses a thick or thin blood smear and most often a Giemsa stain, is the gold standard for confirming a diagnosis of malaria, even though it can take several days and depends on the skills of the laboratory technician. ¹⁶ A thick and thin smear analysis was ordered to confirm the diagnosis and was sent to an outside laboratory per our facility’s laboratory testing protocols.

Of the treatment options recommended by the Centers for Disease Control and Prevention (CDC), the antiarrhythmic quinidine was the only antimalarial medication immediately available in our hospital formulary. ¹⁸ The pharmacy reported that the preferred first-line treatment option, atovaquone-proguanil, was a nonformulary and would arrive in approximately 3 days. Quinine, an alternate treatment option preferred to quinidine per CDC guidelines, was estimated to arrive in 24 hours. The patient was therefore initially started on quinidine sulfate and doxycycline. The following day, the patient was switched from quinidine to quinine. Quinidine is most often indicated for severe, life-threatening cases of malaria caused by Plasmodium falciparum and, thus, was not a recommended first-line treatment option for a patient at this stage of the disease. ¹⁸

Results of malaria microscopy were returned 2 days after admission, confirming a diagnosis of malaria with 1% parasitemia. After atovaquone-proguanil arrived at the hospital pharmacy and was initiated in the patient, quinine was stopped. Testing for glucose-6-phosphatase dehydrogenase (G6PD) deficiency was performed, and the patient was subsequently discharged with a final diagnosis of Plasmodium vivax infection. He was provided with instructions to complete his course of atovaquone-proguanil and primaquine as an outpatient. Individuals with G6PD deficiency are susceptible to autoimmune hemolytic anemia when taking certain medications, including primaquine; thus, patients are tested prior to beginning treatment. ¹⁹

After discharge, the patient completed a 7-day course of atovaquone-proguanil followed by a 14-day course of primaquine. Two months later, our team was able to contact the patient via telephone. He had returned to India to live with his family and was feeling well with full resolution of his symptoms.

Discussion

Our experience suggests that resources to promptly diagnose and treat malaria in the United States are not always readily available. Our case reflects an uncomplicated course of malaria in an urban hospital setting in the South at risk of exposure to the disease because of its proximity to a major port. Despite a straightforward presentation of malaria, confirmation testing of the disease in our patient took more than 48 hours. In addition, even though our team was aware of the treatment protocols and complied with CDC guidelines, our facility lacked the therapeutic capabilities to treat the patient adequately, and it took more than 24 hours to obtain an appropriate medication. Although the patient in this isolated case did not develop any major complications as a result of diagnosis and treatment delay, we must meticulously examine the systems currently in place to prevent poor patient outcomes in the likely event that incidence of vector-borne disease begins to rise, especially in southeastern states.

Unfortunately, this issue in timely case management of uncomplicated malaria is not entirely unique to this hospital. A 2017 nationwide survey of health care provider laboratories found that most US laboratories surveyed had the capability for timely diagnosis of malaria, but only 12% fully comply with Clinical and Laboratory Standards Institute (CLSI) guidelines, causing delays. ²⁰ CLSI guidelines include several requirements for examining blood smears, a recommended availability of diagnostic capabilities 24 hours per day, 7 days per week, and immediate reporting of results to reduce delays in timely diagnosis and reporting. However, we suggest that issues in compliance with CLSI guidelines may be due in part to inexperience and a lack of urgency resulting from a currently low incidence of malaria in the United States. ²⁰ Multiple reported cases of patients with suspected malaria indicate that delays in laboratory confirmation of the disease played a role in delayed diagnosis and, in some cases, death. ²¹ These reports and our case demonstrate that, despite existing guidelines and providers’ knowledge of the disease, as a nation we still lack the capacity to treat malaria in a timely manner and properly protect our patients from potentially harmful complications. Laboratories need to be held to a more rigorous standard for confirmation testing of infectious disease, while hospitals and pharmacies of neighboring regions should develop a supportive network to share medication supplies and ensure rapid delivery.

This delay in laboratory diagnosis confirmation reveals that our health care system may not be prepared to manage an increasing incidence of malaria that can occur with climate change, especially in southern regions most susceptible to changes in weather conditions and expansion of Anopheles populations. As disease patterns continue to shift, our health care system needs to be aware of these changes and be willing to adjust protocols to combat these new challenges. It is imperative to thoroughly examine testing and treatment protocols not only for malaria but for all vector-borne diseases that pose a threat for emergence and reemergence in the United States.

While addressing climate change to prevent a rise in vector-borne disease requires policy interventions at a local, state, and national level, health care providers play an important role in prevention and risk reduction of malaria. As physicians, our role is to ensure that our patients are fully educated on the importance of adhering to prophylactic antimalarial medication regimens, both during and after international travel to endemic regions. It is also crucial to educate patients on proper protection to avoid mosquito bites—by using repellent, wearing long-sleeved clothing, and having screens on windows and doors. In addition, it is important to remind patients to empty outdoor containers that may hold standing water and serve as mosquito breeding sites. Finally, US medical education programs should consider the effects of a changing climate when training health care providers, so that physicians are more likely to keep previously uncommon diseases, such as malaria and dengue, on their list of suspected diagnoses when patients present with otherwise unexplained symptoms.

By thoroughly addressing the gaps in timely diagnosis and treatment of malaria, educating our patients on prevention and risk reduction, and reemphasizing previously uncommon diseases in the medical curriculum, we can strengthen our public defenses against a growing threat of vector-borne diseases as the climate crisis escalates.