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Malaria in Mississippi: history, epidemiology, and current status.


Malaria is one of the most serious human diseases in the world, and more people have died from it than from any other vector-borne disease, and possibly, any other infectious disease in human history. Classic malaria includes symptoms such as fever, chills, sweats, headache, muscle pain, and malaise which may repeat in cycles with high fever and sweating. Infants may display only lethargy, irritability, and anorexia. In rare forms of malaria due to Plasmodium falciparum (e.g., cerebral malaria), chills and fever may be absent, and the patient may present with medical shock, delirium, or coma (Cunnion et al. 1984, Gilles and Warrell 1993). These forms may lead to complications such as renal failure, hemolytic anemia, hypoglycemia, and acute pulmonary edema.

Unfortunately, after more than 100 years of intensive prevention and control efforts, malaria continues to be a major health problem in many areas of the world exacting a huge economic and human health toll (Tsai and Krogstad 1998). The WHO estimates that 350500 million cases and as many as 1-2 million deaths occur from malaria annually (WHO 2005), although recent estimates are a bit lower (Enserink 2010). Despite recent successes with insecticide-treated bed nets and artemisin-based combination therapies (ACT), the malaria situation may actually be worsening due to loss of public health infrastructure from civil strife and large-scale refugee movements, primarily in sub-Saharan Africa, and enhanced susceptibility of the population due to tuberculosis and the HIV/AIDS epidemic (Stillwaggon 2009, Hurtley et al. 2010). In addition, climate change may be resulting in spread of malaria to new areas. For example, malaria has recently spread into highland regions of East Africa where it previously did not exist. This spread presumably occurred because of warmer and wetter weather, resulting in high rates of illness and death because the disease was introduced into a largely nonimmune population (Lafferty 2009, Shuman 2010). Further, there has been development of resistance in the causative agents (Plasmodium spp.) to many of the traditional antimalarial drugs. Public health agencies in countries in Temperate Zones where endemic malaria once existed have to remain diligent to prevent re-introduction and reestablishment of the disease.


Malaria agents and vectors in Mississippi. Historically, human malaria was thought to be caused by any one of four species of microscopic protozoan parasites in the genus Plasmodium--Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium falciparum, although we now know that a fifth species causes human malaria--Plasmodium knowlesi (Collins and Barnwell 2009, Indra 2010, Kantele and Jokiranta 2010). Not all species of Plasmodium occur in all places, nor do they produce identical disease syndromes. Generally, P. vivax is prevalent throughout all malaria-endemic areas, except sub-Saharan Africa, and is the form known for producing relapses. Plasmodium ovale is found chiefly in tropical areas of western Africa (occasionally western Pacific and Southeast Asia). Plasmodium malariae has a wide but spotty distribution around the world and is the most important cause of malaria resulting from blood transfusions. Plasmodium falciparum is the most virulent species and predominates in sub-Saharan Africa, but is also common in Southeast Asia and South America. Plasmodium knowlesi occurs in Southeast Asia and is the species most often associated with long-tailed macaques (although humans can be infected). Historically, malaria cases in Mississippi were primarily due to P. vivax and P. falciparum, and to a lesser extent P. malariae (Carley and Balfour 1929, Faust 1949). In the early 1900's, the American South experienced a peak of malaria transmission, while the disease had been mostly eradicated north of Ohio (Ackerknecht 1945). The South had only one-third of the U.S. population in 1940, but 96% of all reported malaria deaths in the nation (Faust 1941). In 1941, the malaria rate for the U.S. as a whole was 0.1 per 100,000 population, while that for the fourteen southern states was 2.73 (Faust 1942). Heavily endemic malaria foci included the delta area of the lower Mississippi Valley from about Cairo, IL to Natchez, MS (Figure 1) (Faust 1941). In fact, one study of Sunflower and Bolivar Counties in Mississippi from 1916-1918 revealed an estimated 50% prevalence of malaria among the human population (Bass 1919). A large portion of deaths occurring in the Mississippi Delta region at that time was due to malaria, with hemoglobinuria (= bloody urine) and so-called "congestive chills" being the most commonly reported symptoms associated with fatalities (Bass 1927).


Infective malaria sporozoites are transmitted to humans only by mosquitoes in the genus Anopheles. However, not every species of Anopheles is a vector; less than half of the more than 400 known species are considered vectors. In fact, of these, only 45-50 species are important vectors worldwide. It is believed that there are at least four malaria vectors in the United States--Anopheles freeborni (West), An. hermsi (a recently described species in the West), An. punctipennis (West), and An. quadrimaculatus (East). Anopheles quadrimaculatus is a complex of five nearly identical species, although one of them, An. quadrimaculatus sensu stricto was historically the primary species involved in malaria transmission in the southeastern U.S. (Levine et al. 2004). Other Anopheles species may also be capable of malaria transmission in the United States, but are considered vectors of minor importance (Jensen et al. 1998). All four of the main vector species in the U.S. breed in permanent freshwater sites, such as ponds, pools, and rice fields, and are avid human biters.

Evidence identifying the principal vector species was reported in 1929 when Manuel Perez preformed an anopheline survey in the state of Mississippi and found that An. quadrimaculatus, An. punctipennis, and An. crucians (now recognized as a species complex (Wilkerson et al. 2004)) were distributed statewide (Perez 1930). Figure 2 shows a map of Mississippi with the physiographic regions of the State labeled, including the mains ones--the delta, the north-central plateau, the Tennessee-Tombigbee hills, the pine hills (piney woods), and the coastal plain (Lowe 1919). Anopheles quadrimaculatus was most common in the delta and north central plateau where slow moving water sources such as lakes, streams, and ponds are most prominent (Barber and Komp 1929). Anopheles punctipennis and An. crucians were most common in the north-central plateau and pine hills region (Hoffman 1931). These data demonstrated that the distribution of malaria and An. quadrimaculatus overlapped in the South, leading the authors to conclude that this species was responsible for the endemic presence of malaria in that region (Hoffman 1931).


Regional differences/patterns of outbreaks

In the first half of the twentieth century malaria was reported in every county in Mississippi (von Ezdorf 1914). In 1913, return postage paid post cards were sent to physicians in all 79 counties within the State inquiring about the incidence of malaria within their county. In August of that year, 2,009 cards were mailed and 528 were returned representing all 79 counties. Results showed that there were 14,753 cases diagnosed in the month of August and 1,142 of them were confirmed microscopically. Interestingly, of the 528 cards returned, only 136 physicians (representing 50 counties) reported using a microscope to diagnose malaria. This translates to only 26% of physicians using microscopes for diagnosis of malaria during this time (von Ezdorf 1914). This might explain inaccuracies encountered when looking at the incidence of disease among different sources. In 1946, there were approximately 17,000 cases of malaria reported to the Mississippi State Board of Health. However, in the following year fewer than 1,000 cases were reported. The reason for this drastic difference was due to the State requiring that the pathogen be identified in each case and included a $5.00 bounty for each confirmed case (Harden et al. 1967). Perhaps diagnostic techniques prior to 1947 resulted in inaccurately diagnosed cases and thus inaccurate statistics.

Complicating matters, malaria was likely blamed for illnesses that it did not cause. In autumn when a large number of people came down with symptoms of fever and chills, many physicians believed that a microscope was not needed to diagnose malaria and usually they just treated with quinine. Below, a country physician gives his account of suspect malaria cases and their treatment:

"We had ague as a regular disease, and it was not difficult to diagnose. You could feel it with the naked eye. Other people could also feel it when that patient had a chill, for he shook the house. Our standard remedies for ague were calomel, castor oil, and quinine, and they were not measured out on the apothecary's scales." (Busbey 1927)

Furthermore, many people likely never sought medical treatment for malaria and lived with chronic infection for most of their lives. These people would also never have been reported as "cases" and would have contributed to the inaccuracy of malaria incidence reports.

The incidence of malaria also varied by race and various regions of the State. In terms of overall numbers, the disease affected whites more than non-whites, but this was thought to be a result of better reporting (Hoffman 1932). Blacks were generally refractive to P. vivax infection, but susceptible to P. falciparum (Faust 1949). As for death rates, non-whites had decidedly higher numbers (Figure 3), likely due to lack of appropriate healthcare. For example, in 1930, the white death rate from malaria in Mississippi was 10.0 per 100,000, while the black death rate was 17.8 (Hoffman 1932). As mentioned, the highest incidence of malaria in Mississippi occurred in the delta region followed by: bluff, northeastern, southeastern, and the coastal regions (von Ezdorf 1914).

Factors contributing to malaria in Mississippi. Different regions of Mississippi had different factors influencing incidence and prevalence of malaria which must be considered for prevention and control purposes. For example, in many parts of the world, yearly malaria mortality rates correspond with annual rainfall amounts. This was not the case for Mississippi historically. Figure 4 shows the average rainfall compared to total number of malaria deaths within the State. As annual rainfall increased, malaria deaths often decreased and vice versa. Thus, annual rainfall and temperature were apparently not important factors influencing the incidence of malaria. This graph also shows a cyclic occurrence of disease every 5-7 years which cannot be easily explained.

Socio-economic factors seem to better explain the historical incidence of malaria in Mississippi (Brierly 1945). The prevalence of malaria was much higher in rural districts as compared to the larger cities and was thus considered a rural disease. Rural areas had homes that were inadequate with occupants too poor to make improvements to the dwelling. The worst malarious areas had homes that were not owned by the occupants and with occupants who did not remain in the same place very long (Watson and Maher 1941). This was one of many reasons why malaria was so difficult to eradicate (Dowling 1924). In addition, during the 1900's, the livelihood of people living in Mississippi was heavily dependent upon agriculture, with the primary crop being cotton. In the delta, there were large numbers of blacks and whites who occupied poorly constructed "cabins" often situated near swamps and bayous. Further, with the State being so dependent upon the cotton crop, a majority of the people were left with an inadequate food supply when cotton prices were low (Brierly 1945). This suggests that income played a significant role in the health of farmers and their tenants. Income as reported on tax returns is a good indication of the economic condition of the people. Figure 5 shows a strong inverse relationship between the tax return data and malaria deaths over the course of the 22 years, except for 1929 to 1931. As personal income decreased during the depression, the number of deaths from malaria increased and vice versa (Faust 1941, Brierly 1945). Theoretically, during years of high income, people could afford better protection and treatment from the disease such as better clothing, quality food for nourishment, proper screening on houses, medical services, and therapeutic drugs, all of which are important in the health and immunity of people trying to ward off disease.




Elimination of malaria in Mississippi

In 1929, Dr. Felix Underwood, State Health Officer of Mississippi, initiated efforts to make malaria control an integral function of local (county) health departments (Underwood 1929). He believed that temporary or transient disease control workers sent from the federal government were important, but not near as much as trained local personnel who he said, "have not only the basic training, but that indefinable public health viewpoint and sufficient knowledge of economics and sociology peculiar to the territory involved." This was among the first efforts nationwide to establish trained sanitarians in every county to investigate diseases, perform inspections, and conduct general sanitation education and investigations. In the late 1930's, the U.S. Public Health Service established malaria control units within health departments of several southern states so that control efforts could be more organized and systematic (Bradley et al. 1940). The idea was to switch health department malaria control efforts from passive to active--finding and treating every case of malaria (Mountin 1944). Entomologists were also assigned to these units and their duties included basic research, surveillance, and control efforts. Control of malaria seemed to be divided among those who wanted to destroy the vector and those who wanted to treat the parasite within the human host (Humphreys 2001). Control efforts consisted of pesticide use (such as with Paris green), destroying breeding sites, and promoting screen wire for windows (see text box). Screening played a substantial role in malaria prevention as evidenced by increased use in households. For example, in 1905, approximately 5% of houses in Sharkey County, Mississippi had screen doors and windows. By 1931, this number had increased to 64% (Barrier 1932). Control efforts aimed at the parasite included better distribution and use of anti-malarial drugs such as quinine as well as improvements in socioeconomic conditions (Humphreys 2001).

Until 1945, many efforts were implemented which significantly reduced the morbidity and mortality of malaria but never completely eliminated the disease. It is difficult to say for sure which had the largest effect because all may have played a role in the collaborative eradication of the disease from the Unites States. One likely key factor was the switch from passive to active surveillance with an effort to find/treat every case. Interestingly, during times when malaria had decreased or disappeared, there were still large numbers of Anopheles mosquitoes present. This seems to be a factor unrelated to the presence of malaria (Barber 1929). In addition, improved reporting of malaria cases and statistical data helped identify problem areas and locations where control efforts could be focused (Hoffman 1931). Housing for livestock was improved which redirected mosquitoes away from humans. The quality of human dwellings also improved by the mid-1940's and increased personal income allowed for repairs to screening on houses. Education was an additional significant factor which led to prompt recognition and treatment of cases as well as use of screening (Barber 1929). The pesticide, DDT, became widely available for mosquito control in the South after 1945 (Faust 1951). Finally, medical treatment and quinine became more affordable and accessible to citizens. For example, quinine sold for about $4.00 per ounce in 1896, but that fell to about 25 cents per ounce in 1913 (Barber 1929).

Barber stated that, "The factors concerned in the diminution of malaria in the United States are interdependent; their importance has varied with time and locality, but all have been closely related to the agricultural development of the country." Removal of malaria in the South was more likely due to development and enhancement of rural life-styles rather than to campaigns by health agencies (Barber 1929). Improvements of social conditions diminished the malaria threat in spite of the large numbers of Anopheles still present (Barber 1929). The last case of locally-acquired malaria within Mississippi occurred in 1955, with the last death occurring in 1953. Since then, mosquito control efforts have been mainly directed towards practical or nuisance mosquito control, instead of malaria prevention and control (Harden et al. 1967).


Presently in the United States, malaria is generally not thought of as a disease of significant public health concern. In 2005, there were 1,528 cases of malaria reported in the United States (CDC 2005), but the vast majority of these involved persons traveling to and from endemic areas overseas and were thus considered imported cases. Other possible sources of infection within the United States include exposure to infected blood such as transfusions, congenital transmission, or local mosquito-borne transmission, which is rare (CDC 2005). Seventy-four cases of locally acquired or autochthonous malaria were identified in the U.S. between 1957 and 1994; none occurred in Mississippi (Zucker 1996). There were 1-7 cases of malaria reported each year from Mississippi during 2002--2008, approximately half of them due to P. vivax and the other half P. falciparum (CDC 2009, MSDH 2010). The malaria vector in Mississippi, Anopheles quadrimaculatus, is still present, widespread over much of the State, and occurs in relatively high numbers. A recent study collected 12,657 specimens of this species from all months of the year and from 41 Mississippi counties, although it likely occurs statewide (Goddard et al. 2010). Peak activity of An. quadrimaculatus is mid- to late summer.

Treatment. Currently, drugs are primarily used for malaria control in two ways--prevention of clinical malaria (prophylaxis) and treatment of acute cases. Antimalarial drugs include chloroquine, amodiaquine, pyrimethamine, sulfonamides, quinine, quinidine, tetracyclines, mefloquine, and artemisinin (usually in combination with other anti-malarials). Because of increased parasite resistance to antimalarial drugs, treatment regimes have become quite complicated and vary tremendously by geographic region. In addition to the problem of resistance, serious side effects may occur with the use of some antimalarial products. Perhaps the most promising of anti-malarial treatments is artemisinin-based combination therapy (ACT) for countering the spread and intensity of P. falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs (Breman et al. 2004). Health care providers should contact their local or state health department, the CDC, or the preventive medicine department at a local medical school for the most up-to-date malaria treatment recommendations.


Dr. Bruce Harrison, North Carolina Department of Environment and Natural Resources, and Dr. Andrea Varela-Stokes, College of Veterinary Medicine, Mississippi State University, looked at earlier versions of this manuscript and offered valuable suggestions. Dr. David Conwill, Mississippi Department of Health, provided recent malaria case numbers for Mississippi. This article has been approved for publication as Journal Article No. J-11850 of the Mississippi Agriculture and Forestry Experiment Station, Mississippi State University.


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Jerome Goddard, Ph.D. (1) and Kelly Hataway, M.P.H. (2)

(1) Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762

(2) Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762

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Date:Oct 1, 2011
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