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    Prepatent periods for 19 sporozoite-induced reinfections with Plasmodium falciparum.

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    Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with the McLendon strain of Plasmodium falciparum. Patients were previously infected only with the homologous McLendon strain. No drug treatments were given to modify the primary attack.

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    Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with the McLendon strain of Plasmodium falciparum. Patients S-988, S-1034, S-812, S-972, S-1020, and S-814 were previously infected with P. malariae as well as with the homologous McLendon strain ; patient S-864 had been previously infected with P. vivax, and patient S-1326 had been previously infected with P. ovale and P. malariae, as well as with the homologous McLendon strain. No drug treatments were given to modify the primary attack.

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    Asexual parasite counts and episodes of fever during the first 20 days of patent parasitemia in patient S-535 reinfected with the McLendon strain of Plasmodium falciparum after previously being infected twice with P. malariae in addition to the McLendon strain. Patients G-303 , G-350, and S-934 were reinfected with the homologous El Limon strain; patients G-432 and G-400 were reinfected with the homologous El Limon strain after previous infection with P. vivax, P. ovale, and/or P. malariae. No drug treatments were given to modify the primary attack.

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    Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with heterologous strains of P. falciparum. Patients had no history of infection with other species of Plasmodium.

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    Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with heterologous strains of Plasmodium falciparum. Patients also had been infected previously with P. malariae. No drug treatments were given to modify the primary attack.

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    Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 7 patients reinfected with heterologous strains of Plasmodium falciparum. Patient S-1338 also had been previously infected with P. malariae. Patients G-268, S-1274, S-1322, S-1044, S-1295, and S-542 also had been infected previously with P. malariae, P. ovale, and/or P. vivax. No drug treatments were given to modify the primary attack.

  • View in gallery

    Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with heterologous Colombia strain of Plasmodium falciparum. All patients also had been previously infected with P. ovale, P. vivax, and/or P. malariae. Patients had been treated with amodiaquine (A), chloroquine (C), or mepacrine (M), to modify the primary attack.

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    Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 6 patients reinfected with heterologous Thailand strain ( S-1321, S-1324, S-1270, S-1323, and S-1326) or the El Limon strain (S-710) of Plasmodium falciparum. All patients also had been previously infected with P. ovale, P. vivax, and/or P. malariae. Patients had been treated with pyrimethamine (Py), chloroquine (C,) or quinine (Q) to modify the primary attack.

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    A, frequency of fever ≥ 101°F and ≥ 104°F in 59 patients reinfected with homologous and heterologous strains of Plasmodium falciparum. B, frequency of asexual parasitemia ≥ 1 ,000/μl and ≥ 10,000/μl in the 59 patients. C, frequency of gametocytemia ≥ 100/μl and ≥ 1,000/μl in the 59 patients.

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    A, frequency of fever ≥ 101°F of during the first 20 days of patent parasitemia in sporozoite-induced and blood-induced infections in patients during primary infection compared with patients reinfected with Plasmodium falciparum. B, frequency of asexual parasitemia ≥ 1,000/μl for the 3 groups of patients. C, frequency of gametocytemia ≥ 100/μl for the 3 groups of patients.

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    A, frequency o f fever ≥ 104°F during the first 20 days of patent parasitemia in sporozoite-induced and blood-induced infections in patients during primary infection compared with patients reinfected with Plasmodium falciparum. B, frequency of asexual parasitemia #x2265; 10,000/#x03BC;l for the 3 groups of patients. C, frequency of gametocytemia #x2265; 1,000/#x03BC;l for the 3 groups of patients.

    Based on these observations, the introduction of a new strain of this parasite into a population in which P. falciparum is endemic would be expected to result in renewed clinical and parasitologic activity. However, because of the previous exposure, clinical episodes and parasite counts would be expected to be of lower intensity and density ; individual patients would be expected to vary in their response to infection in spite of the length of previous exposure.

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    Asexual parasitemia, gametocytemia, and fever episodes for patient S-S74 initially infected with the Costa strain, then reinfected with the McLendon strain of Plasmodium falciparum on day 137.

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    Asexual parasitemia, gametocyte mia, and fever episodes for patient S-577 initially infected with the McLendon strain, then reinfected with the Costa strain of Plasmodium falciparum on day 139.

  • 1.

    Collins WE, Jeffery GM, 1999. A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity during primary infection. Am J Trop Med Hyg 61: (suppl):419.

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  • 2.

    Young MD, Hardman NF, Burgess RW, Frohne WC, Sabrosky CW, 1948. The infectivity of native malarias in South Carolina to Anopheles quadrimaculatus. Am J Trop Med 28: 303311.

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    Jeffery GM, Eyles DE, Young MD, 1950. The comparative susceptibility of Anopheles quadrimaculatus and two strains of Anopheles albimanus to a Panama strain of Plasmodium falciparum. J Natl Malaria Soc 9: 349355.

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  • 4.

    Eyles DE, Young MD, 1950. The comparative susceptibility of Anopheles albimanus and Anopheles quadrimaculatus to a South Carolina strain of Plasmodium falciparum. J Infect Dis 87: 189193.

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  • 5.

    Young MD, Moore DV, 1961. Chloroquine resistance in Plasmodium falciparum. Am J Trop Med Hyg 10: 317320.

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    Young MD, Contacis PG, Stitcher JE, Millar JW, 1963. Drug resistance in Plasmodium falciparum from Thailand. Am J Trop Med Hyg 12: 305314.

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    Boyd MF, 1945. On difficulties arising in the experimental propagation of falciparum malaria. Am J Trop Med 25: 293306.

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    Earle WC, Perez M, 1932. Enumeration of parasites in the blood of malarial patients. J Lab Clin Med 17: 11241130.

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    Mayne B, Young MD, 1941. The technique of induced malaria as used in the South Carolina State Hospital. Venereal Dis Information 22: 271276.

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  • 10.

    Collins WE, Collins GM, 1962. Methods and techniques for the handling of mosquitoes in human and animal malaria studies. Proceedings of the 49th Annual Meeting of the New Jersey Mosquito Extermination Association, 188195.

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A Retrospective Examination of Secondary Sporozoite- and Trophozoite-Induced Infections with Plasmodium Falciparum: Development of Parasitologic and Clinical Immunity Following Secondary Infection

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  • 1 Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

A retrospective study was made of clinical records to determine parasitemia and episodes of fever of 59 patients reinfected with Plasmodium falciparum for treatment of neurosyphilis, which was considered standard medical care at the time. Records were collected at the National Institutes of Health laboratories in Columbia, South Carolina and Milledgeville, Georgia during the period 1940 to 1963. Nineteen patients were infected via the bites of Anopheles albimanus, An. quadrimaculatus, or An. freeborni mosquitoes; the median prepatent period was 11.5 days. It was evident that clinical immunity, as measured by the frequency of fever, particularly high intensity fever (≥ 104°F), was increased following reinfection. The parasitologic immunity, as measured by the frequency of asexual parasite counts and gametocyte counts, was also evident. In general, in secondary infections with homologous and/or heterologous strains of P. falciparum, fever episodes ≥ 101¿ of and ≥ 104°F were reduced in number, parasitemia was reduced, and gametocyte production was reduced. However, despite long courses of parasitemia during their primary infections, most patients developed fever and, in some cases, high-density parasitemia and gametocytemia following reinfection. The intensity of the secondary response did not appear to be associated with the length of the previous course of parasitemia. In addition, current infection with heterologous strain parasites did not prevent the development of fever or higher density parasite counts following imposition of the new strain of parasite.

Previously,1 we reported on a retrospective study of the clinical records of 318 neurosyphilitic patients who were treated by infection with the El Limon, Santee Cooper, and McLendon strains of Plasmodium falciparum either via sporozoite or trophozoite inoculation. No records indicated that these patients had been infected previously with Plasmodium. Here, we report a similar examination of the clinical records of patients reinfected with homologous and heterologous strains of P. falciparum.

These studies were conducted at the National Institutes of Health laboratories in Columbia, South Carolina and Milledgeville, Georgia during the period 1940 to 1963.

Materials and Methods

Strains of Plasmodium falciparum. McLendon. The McLendon strain was isolated in October 1940 from a patient who was admitted to the South Carolina State Hospital with malaria.2

El Limon. The El Limon strain was isolated from a resident of El Limon, Transisthmian Highway, Panama in 1948.3

Santee Cooper. The Santee Cooper strain was isolated during the summer of 1946 from a person living in the vicinity of the Santee-Cooper water impoundments in South Carolina.4

Colombia. The Colombia strain was isolated in August 1960 from a patient who had apparently acquired his infection in the Magdalena Valley, Colombia.5

Thailand. The Thailand strain was isolated in February 1962 from a U. S. national returning to the United States from Thailand.6

Costa. This parasite was received in the Columbia, South Carolina laboratory in September, 1944 from Dr. Mark Boyd. It was described by Boyd as “of indigenous origin” (i.e., Florida, United States).7

Other strains that had limited study were provided by various investigators.

Methods of inoculation. Patients were infected either by the inoculation of parasitized blood or via sporozoites. With the latter, inoculation was either by the bites of infected mosquitoes or by the subcutaneous or intravenous inoculation of sporozoites dissected aseptically from mosquito salivary glands. In some instances, blood or sporozoites were preserved frozen and thawed immediately before inoculation into the patient.

Parasitemia. Thick and thin peripheral blood films were made daily by the method of Earle and Perez,8 stained with Giemsa, and examined microscopically for the presence of parasites. Asexual and sexual parasites were recorded per microliter of blood. During the later stages of the infection, when parasite counts were very low and no symptoms of malaria were evident, blood films were usually made two or three times a week.

Patient management. Consent for treatment of patients for mental disorders was granted when patients were admitted to the hospitals, either by their families or the courts. The decision to treat a neurosyphilitic patient with malaria was part of routine patient care by the medical staff of the South Carolina State Hospital or the Georgia State Hospital and not for research purposes. Patient care and evaluation of clinical endpoints (e.g., fever) were the responsibility of the medical staff. All patients were housed in screened wards of the hospital to prevent infection of local anophelines. While undergoing paroxysms, the patients were treated symptomatically. During infection, temperature, pulse, and respiration were checked every 4 hr and hourly during paroxysms. Infections were terminated for the following reasons: sudden overwhelming infection with parasites, severe anemia, unremitting pyrexia, rapidly enlarged and tender spleen, extreme exhaustion, cardiac disturbances, cyanosis, edema, convulsions, renal disturbances, marked increase in blood urea, development of another infectious disease, severe jaundice, or rapid debilitation involving weight loss.9

Table 1

Previous malarial experience with Plasmodium falciparum, P. ovale, P. vivax, and P. malariae of 59 patients reinfected with P. falciparum

PatientSpecies/strainDays*Maximum parasitemiaDays of feverNegative interval days
G-228falciparum/Santee Cooper100 32,160 2   15
falciparum/El Limon222 14,040 6
G-268falciparum/Santee Cooper375 29,280  141
ovale/Donaldson 16    0
falciparum/El Limon137 12,980 1
G-303falciparum/El Limon253 43,56017  235
falciparum/El Limon 46 14,97611
G-308falciparum/Santee Cooper136 98,28019 1192
falciparum/El Limon189 35,520 7
G-324falciparum/Santee Cooper102 58,320 4  355
falciparum/El Limon 97 20,700 9
G-350falciparum/El Limon  9 92,160 3  307
falciparum/El Limon362 15,840 5
G-400vivax/Chesson129   36
vivax/Chesson 36    0
falciparum/El Limon 31189,36014  203
vivax/Chesson  9  325
ovale/Donaldson 65   13
malariae/USPHS 34  143
ovale/Liberian 28  160
falciparum/El Limon 49 30,25015
G-432vivax/Chesson121   59
ovale/Donaldson 25  160
falciparum/El Limon 18216,72010  185
ovale/Liberian 32  163
falciparum/El Limon 49 45,36022
S-400falciparum/McLendon 16191,600 7  109
falciparum/McLendon107 43,90013
S-41Ofalciparum/McLendon 56 22,90012  206
falciparum/McLendon  8,200 4
S-522falciparum/McLendon157 24,900 4   32
falciparum/V-49 12  2,960 1
S-535falciparum/McLendon104 34,700 6   77
malariae/USPHS169  487
malariae/USPHS 74    2
falciparum/McLendon 20  4,040 0
S-542malariae/USPHS 44   30
vivaxV-49 86  257
malariae/USPHS  3    8
falciparum/McLendon 58 96,400 6    3
falciparum/Costa 65 15,360 6
S-573falciparum/McLendon132 15,800 3   16
falciparum/Costa105 12,550 3
S-577falciparum/Costa152 41,30012
falciparum/McLendon 97 62,40015
S-707falciparum/McLendon 30 16,25010   83
falciparum/McLendon 11   600 0
S-710vivax/St. Elizabeth 451,176
vivax/St. Elizabeth 47    8
malariae/USPHS 31    0
falciparum/McLendon 34  9,752 53,681
vivax/St. Elizabeth  5  142
falciparum/El Limon191172,27535
S-713falciparum/Santee Cooper108 24,20012    2
malariae/USPHS1202,042
falciparum/McLendon 54  6,180 7
S-715malariae/USPHS 73    0
falciparum/McLendon 90 82,400 8   17
falciparum/Santee Cooper 88  7,750 2
S-734malariae/USPHS172    0
falciparum/Santee Cooper 55   660 1
falciparum/McLendon35+12,65013
S-812malariae/USPHS 22    0
falciparum/McLendon 60 20,620191,483
falciparum/McLendon  9  4,400 5
S-814falciparum/McLendon 18359,200 3    0
malariae/USPHS 15   41
falciparum/McLendon 65 64,440 4
S-830malariae/USPHS149  3,160    0
falciparum/McLendon 41 76,250 6  278
falciparum/El Limon 72  4,420 3
S-864vivax/St. Elizabeth 49   41
falciparum/strain 7 14 31,196 10  444
vivax/Chesson 38    0
falciparum/McLendon 26 15,65016
S-871malariae/USPHS 30    0
falciparum/McLendon 37  6,15010   62
falciparum/Strain 7 50 18,540 6
S-934falciparum/El Limon 12 78,200 4   59
falciparum/El Limon 63 17,05013
S-972falciparum/McLendon 13265,000 7   32
malariae/USPHS 34    8
falciparum/McLendon106  8,94015
S-988falciparum/McLendon 79 28,40016    4
malariae/USPHS 411,803
falciparum/McLendon 83  2,197 7
S-1020malariae/USPHS 70    0
falciparum/McLendon 10 96,960 7   15
falciparum/McLendon  8 17,775 3
S-1034malariae/USPHS 26   26
falciparum/McLendon 69 34,100 7   76
falciparum/McLendon 18  2,300 0
S-1044malariae/USPHS 47    0
falciparum/McLendon 41  7,640 3   15
ovale/Donaldson 18  3,838
falciparum/Colombia108  3,678 4  525
falciparum/Thailand 50    420 0
S-1057vivax/St. Elizabeth 33   74
vivax/Kore 13A 29   68
ovale/Donaldson 412,745
falciparum/McLendon 45 54,48530  428
falciparum/Colombia 66 84,14516
S-1073falciparum/McLendon  9 14,850 5   18
falciparum/McLendon137 35,45023
S-1113falciparum/McLendon 10 28,420 6   52
falciparum/McLendon 11 16,700 0   56
falciparum/McLendon41+  7,040 8
S-1173falciparum/McLendon 22 73,10010   31
falciparum/McLendon125  7,74012
S-1216falciparum/McLendon 14 50,600 8   49
falciparum/McLendon111 36,85012
S-1270falciparum/McLendon152 50,600 8   60
vivax/Chesson 58  929
vivax/Chesson  7   67
ovale/Donaldson 26  597
falciparum/Colombia 55  8,990 3   570
falciparum/Thailand 22 12,487 5
S-1724falciparum/McLendon110 24,480 8   58
ovale/Donaldson 82    0
malariae/USPHS 89  277
falciparum/El Limon 74  4,760 5
S-1295falciparum/McLendon 73 25,92213   68
malariae/USPHS477  981
falciparum/Colombia 55 22,252 2  206
falciparum/Thailand356 12,007 3
S-1319falciparum/El Limon142 52,27019  743
falciparum/Colombia 92  6,561 0
S-1321falciparum/El Limon 98 38,400 5    0
malariae/USPHS 34  716
falciparum/Colombia 23 22,454 4  565
falciparum/Thailand148  3,394 0
S-1322malariae/USPHS241    0
falciparum/El Limon107 21,423 9    0
ovale/Donaldson 32  407
falciparum/Colombia159  6,239 2
S-1323falciparum/El Limon 26476,44010  172
ovale/Donaldson 36    0
malariae/USPHS 23  494
falciparum/Colombia108  9,889 5  501
falciparum/Thailand129 32,280 6
S-1324ovale/Donaldson 23  3,660 2    0
malariae/USPHS 64  663
falciparum/Colombia 58 20,631 5  533
falciparum/Thailand113  6,659 0
S-1326falciparum/McLendon 97 21,42312 0
ovale/Donaldson 49    0
malariae/USPHS 58  155
falciparum/McLendon 46    610 0  292
falciparum/Colombia108 22,049 0  501
falciparum/Thailand108 35,022 5
S-1327ovale/Donaldson 76   38
falciparum/McLendon194 48,140 9   11
falciparum/Colombia  9 88,560 2
S-1328ovale/Donaldson 47  4,200 7    1
falciparum/McLendon176 20,90112   22
falciparum/Colombia101136,081 7
S-1333falciparum/Colombia342 23,95811  317
falciparum/Thailand214 12,848  1
S-1338falciparum/Colombia 50 72,814 9    0
malariae/USPHS 67  527
falciparum/Thailand 67 22,694 5   43
falciparum/El Limon 31 11,242 5
S-1344falciparum/McLendon222 52,11224   23
falciparum/Thailand 84 21,64310

Days of patent parasitemia during previous and current infection with P. falciparum.

Parasites/μl.

Days between termination of primary infection and initiation of secondary infection.

Treatment. Treatment with noncurative doses of antimalarial drugs, usually with low dosages of quinine, was often necessary to modify and control the early stages of the infection with P. falciparum. Infections were terminated by the use of drugs appropriate for the different parasites.

Mosquito feeding. Anopheles quadrimaculatus, An. albimanus, and An. freeborni were the mosquito species used for transmission studies. Mosquitoes were allowed to feed on patients during periods of gametocytemia to be able to infect mosquitoes for transmission to new patients. After the necessary extrinsic incubation period, mosquitoes were fed on patients to induce the new infection. Samples of mosquitoes that had received infective feeding were subsequently dissected to determine the rate and intensity of infection on the midguts and in the salivary glands. In the early studies, small numbers of mosquitoes were contained in glass jars, the ends of which were covered with bobbinet through which the mosquitoes were allowed to feed. In later studies, mosquitoes were contained in paper cartons or plastic cages covered with netting or wire screening. Additional details on the maintenance and infection of mosquitoes have been reported previously.9,10

Figure 1.
Figure 1.

Prepatent periods for 19 sporozoite-induced reinfections with Plasmodium falciparum.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Data presentation. The results of the studies conducted at Milledgeville and Columbia have been combined. Most of the records made before 1 940 were incomplete and were not used. The data presented here are based on those records we consider sufficiently complete to be useful. Fifty-nine patients with a documented history of infection with P. falciparum were reinfected with P. falciparum for the treatment of paresis and other mental disorders associated with tertiary syphilis. Parasitologic and clinical records obtained during these studies were examined to determine the natural course of infection as immunity developed. Signs and symptoms of immunity in untreated patients were taken to be the lessening of episodes of fever and decreases in the parasite count.

Table 2

Maximum parasitemia, days of parasitemia, and days of fever (≥ 101°F and ≥ 104°F) for 19 unmodified and 3 modified infections with Plasmodium falciparum in patients with a previous history of infection with the homologous strain of P. falciparum

Parasitemia*

Previous infectionFeverAsexualGametocytes




Patient no.Spp.Days (+)Maximum paraDay≥101°F≥104°FDays>1,000/μl>10,000/μlDays>100/μl>1,000/μlTreatment§
S-707Pf-McL 30   600 6 0  0 11 0 0 0 0 0
S-1113Pf-McL 10 7,040 5 8  3 41+31 0 41+27 0
Pf-McL 11
S-1173Pf-McL 22 7,740 512125  9 084 20 0
S-410Pf-McL 56 8,200 4 4  0 47+ 9 0 30 1 0
S-1113Pf-McL 1016,700 5 0  0 11 4 2 4118 0Ca     
S-1216Pf-McL 1436,850 712 711132 410129 1Ca     
S-1073Pf-McL  939,450 523  513767 615327 3Bb, Ca
S-400Pf-McL 1643,900 713  410725 7 54 8 0
S-988Pf-McL79 2,197 8 7  2 83 3 0 8221 0
Pm 41
S-1034Pm 26 2,300 5 0  0 18 1 0 41 3 0Ca     
Pf-McL 69
S-812Pm 22 4,400 7 5  0  9 4 0  0 0 0Ca     
Pf-McL 60
S-972Pf-McL 13 8,9401815  110629 011235 0Ca     
Pm 34
S-1020Pm 7017,775 7 3  3  8 6 2 11 0 0Ca     
Pf-McL 10
S-814Pf-McL 1864,440 7 4  1 6716 5 61 1 0
Pm 15
S-864Pv 4915,6501016  9 2611 23819 0Ca     
Pf-McL 14
Pv 38
S-1326Pf-McL 97   610 7 0  0 46 0 0 57 0 0
Po 49
Pm 58
S-535Pf-McL1044 ,040 7 0  0  8 3 0 20 0 0
Pm169
Pm 74
G-303Pf-EL25314,976 811  8 4619 2 24 0 0
G-350Pf-EL  915,840 6 3  2116+22 2136+17 0
S-934Pf-EL 1217,050 713  2 6328 4 611910
G-432Pv12145,360 622  4 4431 7 6429 0Qb, Ca
Po 25
Pf-EL 18
Po 32
G-400Pv12930,2501115  8 4925 6 7231 0Qb     
Pv 36
Pf-EL 31
Pv  9
Po 65
Pm 34
Po 28

Days to last detectable asexual parasite or gametocyte; days of parasite counts > 100, > 1,000, and > 1O,000/μl.

Pf-McL = McLendon strain of P. falciparum; Pm = P. malariae; Pv = P. vivax; Po = P. ovale; Pf-EL = El Limon strain of P. falciparum.

Asexual parasites/μl.

a = treatment to cure infection; b = subcurative treatment to modify primary attack; C == chloroquine; B = proguanil ; Q = quinine

Sporozoite-induced infection.

Two different groups of patients were considered: 1) 22 patients reinfected with homologous strains of P. falciparum, and 2) 37 patients reinfected with heterologous strains of P. falciparum.

The following data were considered for each patient: 1) the presence of fever ≥ 101°F and ≥ 104°F, 2) the presence of asexual parasite counts ≥ 1,000/μl and ≥ 10,000/μl, and 3) the presence of gametocyte counts ≥ 100/μl and ≥ 1,000/μl/μl.

Presented graphically for each patient are 1) the frequency of fever (number of patients with fever/number of patients remaining in study) for each of the first 100 days of patent parasitemia, 2) the frequency of parasite counts ≥ 1,000/μl and ≥ 10,000/μl during the first 100 days of patent parasitemia, and 3) the frequency of gametocyte counts ≥ 100/μl and ≥ 1,000/μl during the first 100 days of patent parasitemia. Prepatent periods for sporozoite-induced infections are also plotted.

The days of maximum parasitemia are presented in tabular form, along with number of days with fever ≥

101°F and ≥ 104°F, length of the asexual parasitemia, (days of parasite counts; ≥ 1,000/μl and ≥ 10,000/μl), and length of the gametocytemia, (days of gameytocyte counts ≥ 100/μl and ≥ 1,000/μl). In addition, drugs used for modifying or terminating the infections are listed. For sporozoite-induced infections, the species of mosquito, the route of inoculation (bites or injection by syringe), the number of mosquitoes or the intensity of the salivary gland infection, and the prepatent periods are given. Intensity of infection of the salivary glands was determined by rating the number of sporozoites at dissection as 1+ (1-1 0 sporozoites), 2+ (11–100 sporozoites), 3+ (101–1,000 sporozoites) or 4+ (> 1,000 sporozoites). The total number of + ratings was then determined.

Figure 2.
Figure 2.

Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with the McLendon strain of Plasmodium falciparum. Patients were previously infected only with the homologous McLendon strain. No drug treatments were given to modify the primary attack.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Results

The 59 patients were divided into 2 groups. Group I consisted of 22 patients reinfected with the homologous strains of P. falciparum. Group II consisted of 37 patients infected with heterologous strains of the parasite. In addition to being previously infected with P. falciparum, some patients had been previously infected with P. malariae, P. ovale, and/or P. vivax, A patient reinfected with P. falciparum more than once was considered a new patient for each reinfection.

Prepatent periods of sporozoite-induced infections. Nineteen of the 59 patients were infected via the bites of An. albimanus, An. quadrimaculatus, or An. freeborni mosquitoes (Table 1 and Figure 1). Prepatent periods for the 5 patients infected with the El Limon strain ranged from 8 to 12 days; one patient infected with the McLendon strain had a prepatent period of 12 days; the 7 patients infected with the Colombia strain had prepatent periods of 11–14 days; the 6 patients infected with the Thailand strain had prepatent periods ranging from 10 to 15 days. The median prepatent period for the 19 patients was 11.5 days.

Group I : reinfection with homologous strain of P. falciparum. Twenty-two patients were reinfected with the homologous strain of P. falciparum (Table 2). Eleven patients had been previously infected with P, falciparum only; 7 had also been infected with P. malariae, and the remaining 4 with P. vivax and/or P. ovale and P. malariae. The length of the previous homologous infection ranged from 9 to 253 days with a mean of 43.9 days. Maximum asexual parasite counts ranged from 600 to 64,4401IlJ with a geometric mean of 16,370/μl The mean length of the asexual parasite count was 58.1 days and the length of parasitemia including gametocytes was 66.1 days,

Seventeen patients were infected and then reinfected with the McLendon strain of P. falciparum (Table 2). Eight of these (S-707, S-1113, S-1173, S-410, S-1113 , S-1216, S-1073, and S-400) had been infected with P. falciparum only (Figure 2); S-1113 had 3 infections with the McLendon strain. Maximum parasite counts ranged from 600 to 43,9001 11-1. During the first 20 days of patent parasitemia, there were 49 days of fever ≥ ’ 101°F; ≥ patients had no fevers ≥ 101°F. S even patients (S-988, S-1034, S-812, S-972, S-1020, S-814, and S-535) had been additionally infected with P. malariae. Maximum parasite counts ranged from 2,197 to 64,440/μl. During the first 20 days of patent parasitemia (Figure 3), there were 26 days of fever; 1 patient (S-1034) had no fever. Three additional patients (S-864, S-1326, and S-535) had more than one previous infection with P. vivax, P. malariae, or P. ovale in addition to their previous infection with the McLendon strain. Maximum parasite counts were 610-15,650/μl (Figures 3 and 4). Patients S-1326 and S-535 had no fevers ≥: 101°F.

Figure 3.
Figure 3.

Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with the McLendon strain of Plasmodium falciparum. Patients S-988, S-1034, S-812, S-972, S-1020, and S-814 were previously infected with P. malariae as well as with the homologous McLendon strain ; patient S-864 had been previously infected with P. vivax, and patient S-1326 had been previously infected with P. ovale and P. malariae, as well as with the homologous McLendon strain. No drug treatments were given to modify the primary attack.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Five patients (G-303, G-350, S-934, G-432, and G-400) were infected and reinfected with the El Limon strain of P. falciparum (Figure 4). Three patients had been infected previously with P. falciparum only, whereas the other 2 patients (G-432 and G-400) had experienced multiple infections P. vivax, P. ovale, and/or P. malariae. Maximum parasite counts ranged from 14,976 to 45,360/μl. During the first 20 days of patent parasitemia (Figure 4), there were 45 days in the which patients had fever ≥ 101°F.

Figure 4.
Figure 4.

Asexual parasite counts and episodes of fever during the first 20 days of patent parasitemia in patient S-535 reinfected with the McLendon strain of Plasmodium falciparum after previously being infected twice with P. malariae in addition to the McLendon strain. Patients G-303 , G-350, and S-934 were reinfected with the homologous El Limon strain; patients G-432 and G-400 were reinfected with the homologous El Limon strain after previous infection with P. vivax, P. ovale, and/or P. malariae. No drug treatments were given to modify the primary attack.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Figure 5.
Figure 5.

Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with heterologous strains of P. falciparum. Patients had no history of infection with other species of Plasmodium.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Table 3

Maximum parasitemia, days of parasitemia, and days of fever (≥ 101°F and ≥ 104°F) for 23 unmodified and 3 modified infections with P. falciparum in patients with a previous history of infection with the heterologous strain of P. falciparum

Parasitemia*

Previous infectionFeverAsexualGametocytes




Patient no.Spp.Days (+)Current infectionMaximum paraDay≥101°F≥104°FDays>1,000/μl>10,000/μlDays>100/μl>1,000/μlTreatment§
S-573Pf-McL132Pf-COS12,55011  3010520  2  6327  0
S-1333Pf-COL342Pf-THA12,848  7  1 021419  4  31  6  0Qa
G-228PF-S-C100Pf-EL14,04012  6222228  121126  0Ca
S-574Pf-COS145Pf-McL20,45013  819918  4    5  0  0
G-324PF-S-C102Pf-EL20,700  7  9  411421  4  9735  0
S-1344Pf-McL222Pf-THA21,6431010  38426  3  8613  0Qa
G-308PF-S-C136Pf-EL35,520  6  7  418930  1191  0  0
S-577Pf-COS152Pf-McL62,40010156973214  5229  0
S-830Pm149Pf-EL  4,420  6  30727  0  7330  0
Pf-McL  41
S-713Pf-S-C108Pf-McL  6,18011  73547  0  4116  0
Pm120
S-715Pm  73PF-S-C  7,75017  20883  0  893515
Pf-McL  90
S-1338PF-COL  50Pf-EL11,242  9  50318  0  4325  0Ca
Pm  67
Pf-THA  67
S-734Pm172Pf-McL12,6501813335+6  1    0  0  0
Pf-S-C  55
S-871Pm  30Pf-718,540  5  635010  1  613712
Pf-McL  37
S-1295Pf-McL  73Pf-COL22,252  9  205520  3  8610  8Ca
Pm477
S-1321Pf-EL  98Pf-COL22,454  9  40236  1  52  3  0Pya
Pm  34
S-1338Pf-COL  50Pf-THA22,69410  51 678  2  7410  0Ab,c, Prc, Qa
Pm 67
G-268Pf-S-C375Pf-EL12,98010  1013716  31383012
Po  16
S-1274Pf-McL110Pf-EL  4,760  6  51744  0  41  7  0
Po  82
Pm  89
S-1322Pm241Pf-COL  6,23923  2015938  017417  0Cc, Ma
Pf-EL107
Po  32
S-1044Pm  47Pf-THA    420  6  0050  0    0  0  0
Pf-McL  41
Po  18
Pf-COL108
S-1295Pf-McL  73Pf-THA12,007  6  3025628  123921  9Qa
Pm477
Pf-COL  55
S-542Pm  44Pf-COS15,360  7  606521  4  6213  0
Pv  86
Pm    3
Pf-McL  58

Days to last detectable asexual parasite or gametocyte; days of parasite counts > 100, > 1,000, and > 10,000/μl.

Pf-McL = McLendon strain of P. falciparum; Pf-COL = Colombia strain of P. falciparum; Pf-S-C = Santee-Cooper strain of P. falciparum; Pm = P. malariae; PF-THA = Thailand strain of P. falciparum; Pf-EL = El Limon strain of P. falciparum; Po = P. ovale; Pv = P. vivax.

Parasites/μl.

a = treatment to cure infection; b = subcurative treatment to modify primary attack; c = subcurative treatment after the primary attack; Q = quinine; C = chloroquine; Py = pyrimethamine; A = amodiaquine; Pr = primaquine; M = mepacrine.

Sporozoite-induced infection.

Group II : reinfection with heterologous strains of P. falciparum. Twenty-three patients reinfected with heterologous strains of P. falciparum were not given treatment with antimalarial drugs to modify their primary infection (Table 3). Eight of these patients (S-573, S-1333, G-228, S-574, G-324, S-1344, G-308, and S-577) had been previously infected with P. falciparum only (Figure 5). Maximum parasitemia ranged from 12,550 to 62,400/μl (Table 3). During the first 20 days of patent parasitemia, there were 46 days of fever ≥ 101°F. Eight of the patients (S-830, S-713, S-1338, S-734, S-871, S-1295, S-1321, and S-1338) also had been infected with P. malariae (Figures 6 and 7). Patient S–1338 was infected first with the Colombia strain, then the Thailand strain, and finally the El Limon strain. Thus, this patient had 2 heterologous reinfections with P. falciparum. Maximum parasite counts ranged from 4,420 to 22,694/μl. During the first 20 days of patent parasitemia, there were 43 days of fever ≥ ’ 101°F. The remaining 6 patients (G-268, S-1274, S-1322, S-1044, S-1295, and S-542) also had been infected with P. ovale, P. malariae, and/or P. vivax (Figure 7). Three patients (S-1338, S-1044, and S-1295) had been infected twice with P. falciparum before their current infection. The length of the previous infection with P. falciparum for these 23 patients ranged from 37 to 342 days with a mean of 127.3 days. Maximum parasite count ranged from 420 to 62,400/μl with a geometric mean of 12,142/μl. The mean length of the asexual parasite count was 101.7 days and the length of parasitemia including gametocytes was 106.6 days.

Figure 6.
Figure 6.

Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with heterologous strains of Plasmodium falciparum. Patients also had been infected previously with P. malariae. No drug treatments were given to modify the primary attack.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Fourteen patients reinfected with heterologous strains of P. falciparum were given treatment with antimalarial drugs to modify their primary attack (Table 4). All but one of the patients also had been infected with P. ovale, P. malariae, and/or P. vivax. The length of the previous infection(s) with P. falciparum ranged from 26 to 25 1 days with a mean of 123.1 days; four of the patients had been infected more than once. Maximum parasite count ranged from 3,394 to 172,275/μl with a geometric mean of 20,69/μl. The mean length of the asexual parasite count was 94.9 days and the length of parasitemia including gametocytes was 111.1 days. Eight of the patients (S-1044, S-1319, S-1270, S-1323, S-1326, S-1057, S-1327, and S-1328) were reinfected with the chloroquine-resistant Colombia strain of P. falciparum (Figure 8). During the first 20 days of patent parasitemia there were 32 days of fever ≥ 101°F. Five patients (S-1321, S-1324, S-1270, S-1323, and S-1326) were reinfected with the multidrug-resistant Thailand strain of P. falciparum. During the first 20 days of patent parasitemia there were 16 days of fever ≥ 101°F (Figure 9). Patient S-710 was reinfected with the El Limon strain (Figure 9); this patient had six fever episodes.

The 59 patients reinfected with homologous and heterologous strains of P. falciparum had 393 fever episodes ≥ 101°F and 120 fever episodes ≥ 104°F. Of the 393 fever episodes, 313 (79.6%) occurred during the first 25 days of patent parasitemia, 42 (10.7%) during the 26-50-day period, 31 (7.9%) during the 51–75-day period, and 7 (1.8%) during the 76–100-day period.

There were 120 days of high-density parasitemia (≥ 10,000/μl) for the 59 patients. Of these, 113 (94.2%) occurred during the first 25 days, 6 (5.0%) during the 26-50- day period, and 1 (0.8%) during the 51-75 -day period.

Figure 7.
Figure 7.

Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 7 patients reinfected with heterologous strains of Plasmodium falciparum. Patient S-1338 also had been previously infected with P. malariae. Patients G-268, S-1274, S-1322, S-1044, S-1295, and S-542 also had been infected previously with P. malariae, P. ovale, and/or P. vivax. No drug treatments were given to modify the primary attack.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

The patients had 92 days of high-density gametocytemia (≥ 1,000/μl). Of these, 70 (76.1%) occurred during the first 25 days of patent parasitemia, 19 (20.7%) during the 26–50-day period, and 3 (3.3%) during the 51–75-day period.

The frequency of fever ≥ 101°F and ≥ 104°F during the first 1 00 days of patent parasitemia (Figure 10A) indicated that only on days 6 and 7 did greater than 50% of the patients have fever ≥ 101°F. The highest percentage of patients (28.8%) with fever ≥ 104°F occurred on day 7.

The frequency of asexual parasitemia ≥ 1,000/μl and ≥ 10,000/μl (Figure 10B) indicated parasitemia ≥ 1,000/μl occurred in 50% of the patients between days 5 and 12. High-density parasitemia (≥ 10,000/μl) was most frequent on day 6 (35.6%).

The frequency of gametocytemia ≥ 100/μl and ≥ 1,000/μl during the first 100 days of patent parasitemia for the 59 patients reinfected with homologous and heterologous strains of P. falciparum is presented in Figure 10C. Gametocyte counts ≥ 100/μl occurred in 50% of the patients between days 14 and 24. High-density gametocytemia (≥ 1,000/μl) was most frequent on day 17 (14.3%).

Discussion

Fifty-nine patients previously infected with P. falciparum were shown to be susceptible to reinfection with homologous and heterologous strains of the parasite. Prepatent periods for sporozoite-induced infections were in the same range as those reported previously for patients following primary challenge.1

Our primary goal was to document the effect of previous malarial experience on secondary parasitologic and clinical responses. In our previous report, patients were divided into 2 groups, i.e., those given treatment with antimalarial drugs to modify the infection and those not given such treatment.1

An examination of the percentage of patients with fever ≥ 101°F (Figure 11A) and ≥ 104°F (Figure 12A) indicated that 50% of reinfected patients had fever ≥ 101°F on days 6 and 7 whereas 50% of patients following primary sporozoite- induced or trophozoite-induced infection had fever ≥ 101°F from day 3 to day 10. When percentages of patients with fever ≥ 104°F were compared (Figure 12A), 25% or greater of patients had fever ≥ 104°F for days 7 and 8, whereas 25% or more of sporozoite-induced and trophozoite- induced primary infections had fever ≥ 104°F on days 3 through 10 and 4 through 10, respectively.

Figure 8.
Figure 8.

Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 8 patients reinfected with heterologous Colombia strain of Plasmodium falciparum. All patients also had been previously infected with P. ovale, P. vivax, and/or P. malariae. Patients had been treated with amodiaquine (A), chloroquine (C), or mepacrine (M), to modify the primary attack.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

An examination of the percentage of patients with parasitemia ≥ 1,000/μl (Figure 11B) and ≥ 10,000/μl (Figure 12B), indicated that 50% of reinfected patients had parasite counts ≥: 1,000/μl on days 5 through 11 whereas 50% of patients following primary sporozoite-induced or trophozoite-induced infection had parasite counts ≥ 1,000/μl from days 3 through 20 and days 3 through 19, respectively. When percentages of patients with parasite counts ≥ 10,000/μl were compared (Figure 12B), 25% or greater of patients reinfected had parasite counts ≥ 10,000/μl for days 6 and 8, whereas 25% or more of sporozoite-induced and trophozoite-induced primary infections had parasite counts ≥ 10,000/μl on days 5 through 18 and 4 through 15, respectively.

An examination of the percentage of patients with gametocytemia ≥ 100/μlrid="fn (Figure 11C) and ≥ 1,000/μl (Figure 12C) during the first 30 days of patent parasitemia indicated that 50% of reinfected patients had gametocyte counts ≥ 100/μl on days 14 through 23 whereas 50% of patients following primary unmodified sporozoite-induced or trophozoite- induced infection had gametocyte counts ≥ 100/μl from days 13 through 30 and days 12 through 30, respectively. When percentages of patients with gametocyte counts ≥ 1,000/μl were compared (Figure 11e), 25% or greater of patients following reinfection had gametocyte counts ≥ 1,000/μl for days 6 and 8, whereas 25% or more of sporozoite-induced and trophozoite-induced primary infections had gametocyte counts ≥ 1,000/μl on days 14 through 28 and 13 through 25 , respectively.

It was evident that clinical immunity, as measured by the frequency of fever, particularly high-intensity fever (≥ 104°F), was enhanced following reinfection. The parasitologic immunity, as measured by the frequency of asexual parasite counts and gametocyte counts, was also evident. Individual patients varied in their clinical and parasitologic responses to reinfection (Figures 2-9). As a group, however, clinical and parasitologic immunity was readily demonstrated.

Of particular interest were the results of reinfection of 2 patients. Patient S-S74 was infected initially with the Costa strain of P. falciparum (Figure 13). During the primary attack, a maximum parasite count of 26,150/μl occurred on day 11 and there were 6 fever episodes between days 6 and 1 6 ; fever of 101°F was also recorded on day 83. On day 137, the patient was reinoculated with McLendon strain parasites. A peak parasite count of 20,450/μl occurred 22 days later associated with 6 days of fever between 16 and 23 days after rechallenge. Patient S-577 was infected initially with the McLendon strain of P. falciparum (Figure 14). During the primary infection, a maximum parasite count of 41,300/μl occurred on day 9, and there were 12 fever episodes between days 6 and 41. On day 139, the patient was reinoculated with Costa strain parasites. A peak parasite count of 62,400/μoccurred on day 162 (23 days later) associated with 6 days of fever between 18 and 23 days after rechallenge. The patient had additional fever on days 68, 84, and 86.

Figure 9.
Figure 9.

Asexual parasite counts and fever episodes during the first 20 days of patent parasitemia in 6 patients reinfected with heterologous Thailand strain ( S-1321, S-1324, S-1270, S-1323, and S-1326) or the El Limon strain (S-710) of Plasmodium falciparum. All patients also had been previously infected with P. ovale, P. vivax, and/or P. malariae. Patients had been treated with pyrimethamine (Py), chloroquine (C,) or quinine (Q) to modify the primary attack.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

The occurrence of these febrile episodes and elevated parasitemia while parasitemia of the initial strain was still patent suggests that the initial infection failed to provide sufficient protection to prevent clinical and parasitologic manifestations of the secondary heterologous strain of parasite. Whether or not the fever was induced as a result of the increased parasite count or differences in the pyrogenic nature of the secondary strain is not known.

Figure 10.
Figure 10.

A, frequency of fever ≥ 101°F and ≥ 104°F in 59 patients reinfected with homologous and heterologous strains of Plasmodium falciparum. B, frequency of asexual parasitemia ≥ 1 ,000/μl and ≥ 10,000/μl in the 59 patients. C, frequency of gametocytemia ≥ 100/μl and ≥ 1,000/μl in the 59 patients.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Table 4

Maximum parasitemia, days of parasitemia, and days of fever (≥ 101°F and ≥ 104°F) for 14 modified infections with Plasmodium falciparum in patients with a previous history of infection with the heterologous strain of P. falciparum

Parasitemia*

Previous infectionFeverAsexualGametocytes




Patient no.Spp.Days (+)Current infectionMaximum paraDay≥101°F≥104°FDays>1,000/μl>10,000/μlDays>100/μl>1,000/μlTreatment§
S-1044Pm  47Pf-COL    3,67811  4  0108100  58  0 0Ab, Cc, Pya
Pf-McL  41
Po  18
S-1319Pf-EL142Pf-COL    6,56115  0  0  92320133  0  0Cb,c, Pya
S-1270Pf-McL152Pf-COL    8,990  5  3  1  26  60  59  0  0Cb, Pa
Pv  58
Pv    7
Po  26
S-1323Pf-EL  26Pf-COL    9,88911  5  210833012647  0Ab, Mc, Pya
Po  36
Pm  23
S-1326Pf-McL  97Pf-COL  22,04912  0  0108262130  0  0Cb, Mc, Pya
Po  49
Pm  58
Pf-McL  46
S-1057Pv  33Pf-COL  84,145  916  4  6623510447  2Ab, HCc, Mc, Pya
Pv  29
Po  41
Pf-McL  45
S-1327Po  47Pf-COL  88,560  7  2  1    9  52  28  0  0Ca
Pf-McL194
S-1328Po  47Pf-COL136,081  7  7  1101214107  4  0Cb, Ac, Ma
Pf-McL176
S-1321PF-EL  98Pf-THA    3,39414  0  0148  40  51  0  0Pyb, Qa
Pm  34
Pf-COL  23
S-1324Po  23Pf-THA    6,659  5  0  011312012316  0Pyb, Qa
Pm  64
Pf-COL  58
S-1270Pf-McL152Pf-THA  12,487  7  5  2  22103  3812  0Qa
Pv  58
Pv    7
Po  26
PF-COL  55
S-1323Pf-EL  26Pf-THA  32,280  9  6  11292711522611Pyb,c, Qa
Po  36
Pm  23
Pf-COL108
S-1326Pf-McL  97Pf-THA  35,022  7  5  3108274109  9  0Qb,a
Po  49
Pm  58
Pf-McL  46
Pf-COL108
S-710Pv  45Pf-EL172,275  93511191  473137  8  0Qb, Cb, Prc
Pv  47
Pm  31
Pf-McL  34
Pv    5

Days to last detectable asexual parasite or gametocyte; days of parasite counts > 100, > 1,000, and > 10,000/μl.

Pm = P. malariae; Pf-McL = McLendon strain of P. falciparum; Po = P. ovale; Pf-EL = El Limon strain of P. falciparum; Pv = P. vivax; Pf-COL = Colombia strain of P. falciparum; PF-THA = Thailand strain of P. falciparum.

Parasites/μl.

a = treatment to cure infection; b = subcurative treatment to modify primary attack; c = subcurative treatment after the primary attack; A = amodiaquine; C = chloroquine; Py = pyrimethamine; P = chloroguanide; M = mepacrine; HC = hydroxychloroquine; Q = quinine: Pr = primaquine.

Sporozoite-induced infection.

In general, in secondary infections with homologous and! or heterologous strains of P. falciparum, fever episodes ≥ 101°F and ≥ 104°F were reduced in number, parasitemia was reduced, and gametocyte production was reduced. However, despite long courses of parasitemia during their primary infections, most patients developed fever and, in some cases, high-density parasitemia and gametocytemia following reinfection, The intensity of the secondary response did not appear to be associated with the length of the previous course of parasitemia, In addition, current infection with heterologous strain parasites did not prevent the development of fever or higher density parasite counts following imposition of the new strain of parasite. However, the 2 patients so reinfected (Figures 13 and 14) had low-density gametocyte counts.

Figure 11.
Figure 11.

A, frequency of fever ≥ 101°F of during the first 20 days of patent parasitemia in sporozoite-induced and blood-induced infections in patients during primary infection compared with patients reinfected with Plasmodium falciparum. B, frequency of asexual parasitemia ≥ 1,000/μl for the 3 groups of patients. C, frequency of gametocytemia ≥ 100/μl for the 3 groups of patients.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Figure 12.
Figure 12.

A, frequency o f fever ≥ 104°F during the first 20 days of patent parasitemia in sporozoite-induced and blood-induced infections in patients during primary infection compared with patients reinfected with Plasmodium falciparum. B, frequency of asexual parasitemia #x2265; 10,000/#x03BC;l for the 3 groups of patients. C, frequency of gametocytemia #x2265; 1,000/#x03BC;l for the 3 groups of patients.

Based on these observations, the introduction of a new strain of this parasite into a population in which P. falciparum is endemic would be expected to result in renewed clinical and parasitologic activity. However, because of the previous exposure, clinical episodes and parasite counts would be expected to be of lower intensity and density ; individual patients would be expected to vary in their response to infection in spite of the length of previous exposure.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

The development of antimalarial vaccines has been based on the identification of epitopes shared by all or most strains of the parasite. The response of these patients to reinfection with homologous and heterologous strains suggests that infection with one strain of parasite confers some level of clinical and parasitologic protection to both homologous and heterologous strains and suggests that induced protection to one strain should have a beneficial effect against challenge with a heterologous strain. Patients who have reached an equilibrium with one strain, resulting in low-density chronic parasitemia with no fever, may be subject to increased parasite counts and renewed episodes of fever when a new strain is superimposed. This is a different pattern of response from the normal development during long-term infection when recrudescent parasitemia occurs. During recrudescence, parasitemia usually fails to reach high density and seldom results in high levels of fever. This suggests a greater level of immunity to variants developing during chronic infection than newly introduced strains or variants.

Figure 13.
Figure 13.

Asexual parasitemia, gametocytemia, and fever episodes for patient S-S74 initially infected with the Costa strain, then reinfected with the McLendon strain of Plasmodium falciparum on day 137.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

Figure 14.
Figure 14.

Asexual parasitemia, gametocyte mia, and fever episodes for patient S-577 initially infected with the McLendon strain, then reinfected with the Costa strain of Plasmodium falciparum on day 139.

Citation: The American Society of Tropical Medicine and Hygiene 61, 1_Supplement; 10.4269/tropmed.1999.61-020

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Author Notes

Authors' addresses: William E. Collins, Division of Parasitic Diseases, Centers for Disease Control and Prevention, Mailstop F-12, 4770 Buford Highway, Atlanta, GA 30341-3724. Geoffrey M. Jeffery (Public Health S ervice, retired), 1093 Blackshear Drive, Decatur, Ga 30033.

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