JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
controversies in malaria chemoprophylaxis and the quest for a malaria vaccine included expert perspectives, review articles, descriptive epidemiological studies, comparative analyses of various malaria chemoprophylaxis strategies, and double- blind randomized controlled trials of candidate vaccines. Articles excluded from review included individual case reports and clinical-pathological conference reports. These selected methodologies met all recommended criteria for narrative reviews including several keywords, use of two or more search engines, defined study period, and article inclusion and exclusion criteria. 3
Rather than analyzing NMSS data based on the laboratory diagnoses of malaria, Khuu and coinvestigators analyzed Nationwide Inpatient Sample (NIS) data based on hospital discharge records for malaria-related hospitalizations over the reporting period, 2000-2014. 2 There were 22,029malaria-related hospitalizations over this period for an annual mean of 1,469 cases and a prevalence rate of 4.88 cases per one million persons per year (CI = 4.50-5.26). There were 182 inpatient deaths and 4,823 severe malaria cases. One or more of the following criteria defined severe malaria: cerebral malaria, renal failure, severe anemia, adult respiratory distress syndrome (ARDS), jaundice, or need for exchange transfusion. Malaria with renal failure was the most common complication (9.6%). P. falciparum was responsible for the majority (72.9%) of malaria-related hospitalizations, followed by P. vivax (22.4%), P. malariae (3.1%), and P. ovale (2.8%). The South (37.1%) and the Northeast (34.2%) had the highest numbers of malaria-related hospitalizations. Khuu and coauthors concluded that the results of their study supported both underreporting and under-ascertainment of malaria cases and deaths by passive surveillance systems such as NMSS. 2 The Life Cycle of the Plasmodium Parasites of Malaria The life cycle of malaria parasites involves a complex natural ecology that requires sequential infections of two living hosts, a human and a female Anopheles mosquito (Figure 2). In humans, infection begins as the mosquito inoculates sporozoites into the circulation. Sporozoites enter liver cells within an hour (hepatic stage) and multiply asexually into schizonts (exoerythrocytic schizogony) which rupture within one to two weeks and release thousands of merozoites into the circulation causing paroxysmal fevers and muscle pains. Merozoites of all species invade red blood cells and utilize hemoglobin as energy substrates to asexually multiply forming trophozoites or ring forms that mature into schizonts (erythrocytic schizogony) and later rupture releasing more merozoites into the bloodstream to invade other red blood cells or to differentiate into sexual forms (gametocytes). In themosquito stage of themalaria life cycle (sporogenic stage), a female Anopheles mosquito ingests male (microgametocytes) and female (macrogametocytes) gametocytes during a blood meal that mate in the mosquito’s midgut (sporogony) as microgametocytes penetrate macrogametocytes to form ookinetes within about 10 days that incubate oocysts. Sporozoites released by oocysts migrate to the salivary glands perpetuating the parasite’s life cycle. The Sites of Action of Antimalarials in the Parasite’s Life Cycle All antimalarial medications used for either prophylaxis or treatment will interrupt specific phases within the human stages of the malaria life cycle. The sites of action of antimalarials in the parasite’s life cycle determine the duration of chemoprophylaxis before and, especially, after travel. Some of the most effective prophylactic medications for malaria will interrupt both exoerythrocytic (hepatic) and erythrocytic (blood) human
RESULTS
The Epidemiology of Malaria in the United States Today Short-term travelers to malaria-endemic countries may be divided into 3 groups: (1) business and conference travelers; (2) tourists; and (3) immigrants returning to their native homelands to visit friends and relatives (VFR). 4 VFR travelers import more cases of malaria into the U.S. than business travelers and tourists for 3 main reasons: (1) avoidance of chemoprophylaxis; (2) prolonged travel to highly endemic inland, rural areas; and (3) a commonly held mistaken belief that lifelong immunity to malaria continues after their immigration. In the U.S., malaria is a nationally notifiable disease that must be reported to health authorities via the National Malaria Surveillance System (NMSS), a passive surveillance system for malaria. NMSS legislation defines cases as malaria confirmed by positive blood films in the laboratory. Local or state health departments then conduct case investigations and transmit reports to the Centers for Disease Control and Prevention (CDC) viaNMSS. Table 1 compares theNMSS-reported trends inmalaria cases by acquisition, transmission, and infecting Plasmodium species over the reporting period, 2004-2013. On average; there were about 1,700 cases per year with P. falciparum causing more than half of all cases annually followed by P. vivax that caused about 18% of cases. 5-10 There were approximately six fatal cases per year with most fatalities caused by P. falciparum or by uncommon mixed infections, usually P. falciparum and P. vivax. Congenital transmission was usually reported every other year. Transfusion, organ transplant, nosocomial, laboratory accident-acquired, and cryptic or unexplained cases of malaria were very rarely reported. The NMSS case definition of malaria is malaria confirmed microscopically by positive smear or molecularly by polymerase chain reaction (PCR). Based on this case definition, the underreportingofmalariamayoccur during thehepatic stages of P. vivax and P. ovale that do not cause acute symptomaticmalaria. Other causes of underreporting may include a failure to identify parasitic stages in peripheral blood smears by inexperienced microscopists, and misdiagnoses of malaria as babesiosis with similar-appearing ring forms. Antimalarial therapy alone is ineffective for babesiosis, and such a misdiagnosis with therapeutic failure should be recognized quickly and corrected.
132 J La State Med Soc VOL 169 SEPTEMBER/OCTOBER 2017
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