Performance of the OptiMAL assay for detection and identification of malaria infections in asymptomatic residents of Irian Jaya, Indonesia.

The OptiMAL assay, a new immunochromatographic "dipstick" test for malaria based on detection of Plasmodium lactate dehydrogenase (pLDH), is purported to detect infections of approximately 200 parasites/microL of blood and to differentiate between Plasmodium falciparum and non-P. falciparum. We evaluated OptiMAL performance by comparing the test strip interpretations of two independent readers with consensus results obtained independently by expert malaria microscopists. Unbiased measures of sensitivity were derived by applying the OptiMAL test for detection and differentiation of light, asymptomatic infections by P. falciparum and Plasmodium vivax. OptiMAL readings were separated in time to determine whether the reaction signal was stable. Microscopy identified infections in 225 of 505 individuals screened; those with P. falciparum (n = 170) averaged 354 asexual forms/microL and P. vivax/Plasmodium malariae (n = 112) averaged 216 asexual forms/microL of blood. Concordance between OptiMAL and microscopy was 81% and 78% by the two independent readings. The assay's sensitivity for detection of any malaria species was 60.4% and 70.2% respectively and specificity was 97% and 89%. Most cases identified by microscopy as P. falciparum were graded as negative or non-falciparum by both OptiMAL readers. OptiMAL false negatives as well as misidentifications were related to low parasitemias (< 500/microL). The OptiMAL assay demonstrated 88-92% sensitivity for detecting infections of 500-1,000 parasites/microL, a range covering the mean parasitemia of primary symptomatic P. falciparum infections in malaria-naïve Indonesian transmigrants. This device was markedly less sensitive than expert microscopy for discriminating between malaria species and is presently unsuited for use as an epidemiological screening tool. The OptiMAL assay is not approved for diagnostic use but is commercially available for research purposes only.

Plasmodium falciparum mdr1 mutations and in vivo chloroquine resistance in Indonesia.

Mutations in the Pfmdr1 gene are reported to be associated with chloroquine resistance in some Plasmodium falciparum isolates. A polymerase chain reaction/restriction fragment length polymorphism method was used for the detection of Pfmdr1 mutations in chloroquine-resistant field isolates of P. falciparum collected in Irian Jaya. The frequency of Pfmdr1 mutations was significantly higher in chloroquine-resistant P. falciparum parasites than background frequencies observed in the same location. The 7G8 mutation was identified in some parasites although always in a mixed genotype status. Chloroquine-resistant P. falciparum specimens were characterized using the World Health Organization 28-day criteria, supplemented by demonstrating adequate chloroquine absorption and genetic analysis.

Lymphocyte response to tetanus toxin T-cell epitopes: effects of tetanus vaccination and concurrent malaria prophylaxis.

Synthesized T-cell epitopes of tetanus toxin are universally immunogenic and serve to enhance immune response when they are used as vaccine carriers of B-cell epitopes. The immunogenicity of the P2, P30, and P2P30 T-cell epitopes of tetanus toxin and whole tetanus toxoid (TT) was evaluated by in vitro proliferation assay of lymphocytes from men with no history of tetanus vaccination who were enrolled in a malaria prophylaxis trial. The enhancement of immune response by tetanus vaccination (Td) and possible antagonism by the antimalarial drugs, was measured by pre- and post-Td comparisons within and between immunized prophylaxis groups (primaquine, chloroquine, placebo) and a nonimmunized control group. Constructs demonstrated low immunogenicity relative to TT in all groups. Relative to both control and its own baseline, the immunized primaquine prophylaxis group was distinct in demonstrating significantly increased proliferation against all three subunits and at both high (30 microg ml(-1)) and low (3 microg ml(-1)) concentrations. Immunization elicited significantly increased proliferation responses by placebo and chloroquine prophylaxis groups against only the P2P30 construct. Despite these significant post-Td changes, a low concentration of TT 0.1 microg ml(-1)) stimulated proliferation 7-10 times over that induced by the greatest concentration of the constructs.

Age-dependent susceptibility to severe disease with primary exposure to Plasmodium falciparum.

This study investigated the incidence of severe disease following primary exposure to Plasmodium falciparum by nonimmune children and adults in Irian Jaya, Indonesia. Four months after arrival, the cross-sectional prevalence of P. falciparum was 72%, and the monthly cumulative incidence of clinical diagnoses of malaria was 81%. Delirium or unconsciousness prompted evacuation to the hospital. Records of emergency evacuation of persons with a clinical diagnosis of malaria revealed an incidence density among adults (>15 years) of 1.34 events/person-year in the third month, whereas the rate in children remained stable at approximately 0.25 events/person-year (relative risk = 4.51, 95% confidence interval [CI] = 1.94-11). Through the first 6 months of exposure, 23.2% of adults were evacuated to the hospital with a diagnosis of malaria compared with 8.6% of children (relative risk = 2.7, 95% CI = 1.9-3.8). In this population with relatively few infants or people of advanced age, the risk of severe disease following primary exposure to P. falciparum increased with age.

Humoral immune response to tetanus-diphtheria vaccine given during extended use of chloroquine or primaquine malaria chemoprophylaxis.

Immune suppression resulting from prolonged chemoprophylaxis and potential drug-vaccine interaction were investigated within the context of a randomized placebo-controlled trial that compared daily primaquine or weekly chloroquine administration for malaria prevention. After 11 months of prophylaxis, adult male subjects received a tetanus-diphtheria (Td) vaccination. Prophylaxis continued 4 weeks longer. Anti-tetanus and anti-diphtheria antibody levels were measured by ELISA at baseline and at 1, 3, 7, and 14 months after Td vaccination. All groups were comparable at baseline. Immunization triggered significant increases in anti-tetanus and anti-diphtheria IgG levels over each group's pre-Td baseline levels and those of an unvaccinated control group. Geometric mean anti-tetanus titers (GMTs) in the primaquine group were significantly higher than those of the placebo group at 1, 3, and 14 months. Anti-tetanus GMTs in placebo and chloroquine groups declined over 14 months to levels comparable to those of unvaccinated controls, but levels in the primaquine group remained significantly higher than in controls.

Intestinal parasite infections after extended use of chloroquine or primaquine for malaria prevention.

Comparative results of baseline and endpoint screening for intestinal parasites are reported from Javanese men enrolled in a year-long, placebo-controlled malaria prophylaxis trial in Irian Jaya. The objective was to detect nontarget qualitative changes that may have resulted from prolonged chloroquine (300 mg base weekly) or primaquine (0.5 mg base/kg daily) prophylaxis. Fresh fecal specimens were examined (blinded trial) for parasites and ova using a modified Kato-Katz thick smear method. More than 88% (94/106) of the baseline population was infected by 1 or more parasite species of which hookworm and Blastocystis hominis were dominant. Paired comparison between baseline and endpoint revealed no significant changes within the primaquine or chloroquine groups with regard to the variety of species found, the mean number of species or ova/subject, the relative proportion of infections caused by these species, or the occurrence of parasite-free, single, and multiple infections. Relative to placebo, there was a significantly greater proportion of infections by Entamoeba histolytica/dispar and a lower mean hookworm egg count in the chloroquine group. The endpoint proportion of new or increased infections in the primaquine group was significantly lower than that of the chloroquine group but comparable to that of the placebo. Despite the dosage employed, the frequency and duration of use, and excretion primarily through the bowels as the active parent compound, primaquine appeared to have little or no significant effect against a variety of common intestinal parasites. These largely negative results lend support for the safety and acceptability of primaquine as a daily malaria prophylactic in a population frequently at risk of intestinal helminth infections.

Impact of epidemic influenza A-like acute respiratory illness in a remote jungle highland population in Irian Jaya, Indonesia.

A suspected epidemic of unknown etiology was investigated in April/May 1996 in the remote jungle highlands of easternmost Indonesia. Trend analysis demonstrates the area-wide occurrence of a major respiratory infection outbreak in November 1995 through February 1996. The monthly mean rate of respiratory infection episodes for the peak outbreak months (2,477 episodes/100,000 persons) was significantly higher (P < .0001) than for the 34 months leading up to the outbreak (109 episodes/100,000 persons). Notable were the high attack rates, particularly among adults: 202 episodes/1,000 persons aged 20-50 years in one community. Excess morbidity attributed to the outbreak was an estimated 4,338 episodes. The overall case-fatality rate was 15.1% of outbreak cases. Laboratory evidence confirmed the circulation of influenza A/Taiwan/1/86-like viruses in the study population, and high hemagglutination inhibition titer responses were indicative of recent infections. Historical documents from neighboring Papua New Guinea highlight the role of influenza A virus in repeated area outbreaks.

Lymphocyte response to tetanus toxoid among Indonesian men immunized with tetanus-diphtheria during extended chloroquine or primaquine prophylaxis.

Immune suppression, a potential side effect of long-term chemoprophylaxis, was evaluated as part of a randomized, placebo-controlled trial that compared daily primaquine against weekly chloroquine for malaria prevention. In the last month of the year-long trial, baseline in vitro lymphoproliferative responses to tetanus toxoid were measured, and a tetanus-diphtheria (Td) immunization was administered. Proliferative responses to tetanus toxoid in each Td-immunized group increased significantly over pre-Td baselines and those of the unvaccinated control. Highest initial responses were measured in the primaquine group. The proportion of responders and the magnitude of proliferation was consistently low in the chloroquine group, and end point responses in this group were significantly below those of the placebo. These results suggest that the development and duration of the cellular response to tetanus immunization was impaired by long-term weekly chloroquine prophylaxis, while daily primaquine prophylaxis over the same time period had no inhibitory effect.

Whole blood chloroquine concentrations with Plasmodium vivax infection in Irian Jaya, Indonesia.

Whole blood concentrations of self-administered chloroquine (CQ) and its metabolite desethylchloroquine (DCQ) were measured in 168 patients with microscopically confirmed infection by Plasmodium vivax in northeastern Irian Jaya, Indonesia. The study consisted of both survey and passive case detection in four separate villages between 1992 and 1994. The subjects were Javanese people 4-51 years old who had lived in the Arso region for up to two years. The sum of CQ and DCQ ranged from 0 to 8,342 ng/ml of whole blood, and 122 subjects (73%) had > or = 100 ng/ml of CQ plus DCQ, the estimated minimally effective concentration (MEC) in whole blood against chloroquine-sensitive P. vivax. Among 56 subjects reporting to a clinic with symptoms of malaria, 53 (95%) had ordinarily effective levels of chloroquine in blood. Among 109 largely asymptomatic malaria patients found by survey case detection, 69 (63%) had chloroquine blood levels greater than the MEC. Virtually all clinical and most subclinical vivax malaria in this region occurs despite ordinarily effective levels of chloroquine in blood.

In vivo resistance to chloroquine by Plasmodium vivax and Plasmodium falciparum at Nabire, Irian Jaya, Indonesia.

A survey of resistance to chloroquine by Plasmodium vivax and P. falciparum was conducted during May 1995 at three mesoendemic villages 30 km southeast of Nabire, near the central northern coast of Irian Jaya, Indonesia. The prevalence of malaria at Urusumu (n = 157), Margajaya (n = 573), and Topo (n = 199) was 18%. 9%, and 9%, respectively, with spleen rates among children of 79%, 10%, and 27%. Infected patients among those screened formed a study population of 64 subjects eligible for a 28-day in vivo test of resistance to chloroquine. Sixty-three patients successfully completed the test; 45 males and 18 females 1-60 years of age, of whom 29 were Javanese transmigrants of five years residence in Irian Jaya and 34 were native to Irian Jaya. The seven-day day cumulative incidence of therapeutic failure for P. vivax and P. falciparum was 15% (n = 34) and 30% (n = 37). The 14- and 28-day estimates of cumulative incidence were 45% and 64% for P. vivax and 58% and 89% for P. falciparum. Almost all recurrences appeared in the face of ordinarily effective levels of chloroquine and its major metabolite, desethylchloroquine, in whole blood (> or = 100 ng/ml). Four infections by P. malariae in subjects enrolled in this study cleared by day 2 and none reappeared within 28 days. Chloroquine no longer provides effective therapy for falciparum or vivax malaria along the northern coast of Irian Jaya, Indonesia.

Malaria in a nonimmune population after extended chloroquine or primaquine prophylaxis.

Extended chemoprophylaxis against endemic malaria raises concern with regard to susceptibility after ceasing use of the drug. In this study, we measured attack rates of malaria among adult men for 28 weeks after they ended one year of prophylaxis using either weekly chloroquine (5 mg base/kg, n = 20), daily primaquine (0.5 mg base/kg, n = 30), or a placebo of primaquine (n = 41). The 28-week incidence densities, times to parasitemia, parasite densities, and symptoms of primary post-prophylaxis infections were not significantly different among the former primaquine, chloroquine, and placebo groups. However, the incidence of Plasmodium falciparum infection in the post-chloroquine group was significantly greater than in the post-primaquine group during the first (P = 0.03) and second (P = 0.02) months post-prophylaxis. Six of 10 primary P. falciparum and three of 10 P. vivax infections occurred in the former chloroquine group within one month after ending prophylaxis and the mean time to infection was 30-35 days. In contrast, only one P. falciparum and no P. vivax infections occurred during the first month after ending primaquine prophylaxis. The mean time to first parasitemia by either species of malaria parasite in this group was 72-77 days. There was no indication that daily use of primaquine for one year placed subjects at greater risk of malaria infection or to more severe clinical symptoms of malaria than subjects who had taken placebo or chloroquine, despite the potential for some degree of immunity to have been acquired in these latter two groups during the year-long prophylaxis period. The results do suggest that chloroquine suppressed P.falciparum infections until drug levels decreased, and that primaquine had effectively prevented the establishment of liver-stage parasites.

Halofantrine and primaquine for radical cure of malaria in Irian Jaya, Indonesia.

The combination of halofantrine and primaquine therapies was calculated as a regimen for achieving radical curve of falciparum or vivax malaria in Irian Jaya, Indonesia, and compared with combined chloroquine and primaquine therapies. The patients who volunteered for the study [adult, male, Indonesian immigrants with no previous exposure to endemic malaria, normal glucose-6-phosphate dehydrogenase (G6PD) activity, uncomplicated malaria illness, no prior use of antimalarials, and parasitaemias of 0.001%-1.1%] were randomized to receive either halofantrine (24 mg base/kg bodyweight, in three equal doses over 12 h) or chloroquine (25 mg base/kg bodyweight over 48 h, in doses of 10, 10 and 5 mg base/kg at 24-h intervals). Each patient also received concurrent daily primaquine (0.5 mg base/kg bodyweight) for 14 days followed by the same dose on alternate days to day 28. A recurrent parasitaemia during the 28 days of follow-up constituted drug failure. Of the 40 cases of falciparum malaria and 26 cases of vivax malaria treated with halofantrine-primaquine, none had a recurrent parasitaemia (100% efficacy). In contrast, 20 of 30 patients with falciparum malaria and three of 27 with vivax malaria had recurrent parasitaemias after chloroquine-primaquine, giving efficacies of 33% and 89%, respectively. Halofantrine-primaquine was significantly more effective than chloroquine-primaquine against falciparum malaria (P < 0.001) but was similarly efficacious against vivax malaria (P = 0.23). On average, fever associated with falciparum or vivax malaria cleared 17 h faster with halofantrine-primaquine (P < 0.01) although there were no significant differences (P > 0.4) in parasite-clearance times between the two regimens. The halofantrine-primaquine regimen was also associated with a more rapid and significant decline in malaria-related physical complaints.

Comparative performance of the ParaSight F test for detection of Plasmodium falciparum in malaria-immune and nonimmune populations in Irian Jaya, Indonesia.

A comparison was made of the performance of the ParaSight F test (F test) for detection of Plasmodium falciparum in blood from malaria-immune (410 native Irianese) and nonimmune (369 new transmigrants) populations in Irian Jaya, Indonesia, where malaria is hyperendemic and all four species of human malaria occur. There were highly significant differences between populations in the sensitivity (Irianese, 60% versus transmigrants, 84%; P < 0.001) and specificity (Irianese, 97% versus transmigrants, 84%; P < 0.001) of the F test. The test had comparably high levels of sensitivity for Irianese children aged < or = 10 years, both age groups of transmigrants (76-85%), but low sensitivity for Irianese aged > 10 years (40%), among whom only 7% of parasitaemias < 120 per microliter and 69% of those > 120 per microliter were detected. Specificity was comparably high for transmigrant children aged < or = 10 years and both age groups of Irianese (93-98%). The low specificity for transmigrants aged > 10 years (79%) was due to a preponderance of false positives, frequently identified by microscopy as P. vivax. The results suggest that comparison based on microscopy underestimated the performance of the ParaSight F test and that malaria immune status, irrespective of P. falciparum density, may influence the test's sensitivity.

PIP: The ParaSight F test uses a nonmicroscopic dipstick approach to the rapid detection of Plasmodium falciparum in blood. The performance of this test was assessed in serum samples collected in Irian Jaya, Indonesia, from 410 native Irianese (malaria-immune) and 369 new transmigrants (nonimmune). Of particular interest was the capability of the F test to detect P. falciparum prevalence among children, whose immunity is less than that of adults. There were highly significant differences by population in the F test's sensitivity (60% for Irianese vs. 84% for transmigrants) and specificity (97% for Irianese vs. 84% for transmigrants). The test had high sensitivity levels (76-85%) for Irianese children 10 years of age and under and both child and adult transmigrants, but low sensitivity (40%) for Irianese over 10 years of age. Specificity was comparably high (93-98%) for transmigrant children and both age groups of Irianese. The low specificity (79%) for transmigrants over 10 years of age reflected a preponderance of false positives, frequently identified by microscopy as P. vivax. These findings suggest that microscopy comparisons underestimate the performance of the ParaSight F test and that malaria immune status, regardless of P. falciparum density, may influence the test's sensitivity.

Lymphocyte proliferative response and subset profiles during extended periods of chloroquine or primaquine prophylaxis.

Immune suppression and disturbances of normal leukocyte populations are side effects attributed to many antimalarial drugs and were concerns during a recent year-long placebo-controlled trial that compared daily primaquine (0.5 mg of base per kg of body weight per day) with weekly chloroquine (300 mg of base one time per week) for malaria prophylaxis. The study took place in Irian Jaya, Indonesia, from July 1994 to August 1995 and enrolled 129 Javanese men with normal glucose-6-phosphate dehydrogenase function. Tests for lymphocyte function and subset composition were conducted blindly on a cross-section of subjects during weeks 10 (n = 42) and 48 (n = 72) of supervised prophylaxis. Lymphocyte function, measured as the proliferative response of peripheral blood mononuclear cells to a panel of mitogens (pokeweed mitogen, phytohemagglutinin, and concanavalin A) and antigens (purified protein derivative of Mycobacterium tuberculosis and Clostridium tetani toxoid) and expressed as a stimulation index, allowed for statistical comparison between groups and sampling times. The lymphocyte subset composition for each group and time point was based on flow cytometry profiling, and the results were expressed as the mean percentages of CD3 (total T cells), CD19 (total B cells), CD4+ (T-helper and inducer cells), and CD8+ (T suppressor and cytotoxic cells), CD3/CD16+ CD56 (natural killer cells), CD3/anti-HLA-DR (activated T cells) cells and the CD4+/CD8+ ratios. Lymphocyte stimulation indices were statistically comparable among the placebo, primaquine, and chloroquine groups at both time points, although the primaquine group was distinguished by having repeatedly greater proportions of subjects with high ( > 3.0) stimulation indices. The lymphocyte subset profiles of these groups at both time points were also similar and undistorted relative to those of healthy reference populations matched for age, sex, and ethnicity. The results provide quantitative support for the safety of daily primaquine prophylaxis.

Treatment of chloroquine-resistant Plasmodium vivax with chloroquine and primaquine or halofantrine.

Optimal therapy for infection by chloroquine-resistant Plasmodium vivax has not been established. From 1992 to 1994 during three separate studies, 147 Javanese residents of Irian Jaya infected by P. vivax were treated with either chloroquine (25 mg of base/kg during 3 days or 10 mg of base/kg in one dose) plus primaquine (10 mg/kg during 28 days or 2.5 mg/kg during 3 days) (n = 78), chloroquine plus placebo (n = 50), or halofantrine (24 mg base/kg in 12 h; n = 19). There was no difference in tolerance to or side effects of any of the regimens. Within 14 days of starting therapy, therapeutic failure among these patients was 44% for chloroquine, 5% for chloroquine plus primaquine (P < .001), and 0 for halofantrine (P < .001). After 28 days, therapeutic failure was 78%, 15%, and 6%, respectively. Thus, chloroquine plus primaquine in combination and halofantrine alone are effective therapies for chloroquine-resistant P. vivax.

Primaquine for prophylaxis against malaria among nonimmune transmigrants in Irian Jaya, Indonesia.

A comparison of primaquine versus chloroquine for prophylaxis among nonimmune transmigrants from Java and Bali in the hyperendemic Arso region of Irian Jaya, Indonesia was conducted. Forty-five subjects received 0.5 mg of primaquine base/kg of body weight every other day, and 54 people in the same village received weekly 5 mg of chloroquine base/kg for 16-19 weeks beginning in December 1992. Plasmodium falciparum accounted for 18 of 30 infections with chloroquine, and four of five infections among subjects receiving primaquine. Plasmodium vivax was found in 12 people taking chloroquine but in just one person taking primaquine. The risk of malaria among people taking chloroquine relative to that among subjects taking primaquine was 3.96 (P = 0.014) for P. falciparum and 10.56 (P = 0.012) for P. vivax. Primaquine was better tolerated than chloroquine. The minimal protective efficacy for primaquine prophylaxis was 74% against P. falciparum and 90% against P. vivax among nonimmune children and adults living in Irian Jaya. These findings require confirmation with randomized, double-blinded, and placebo-controlled trials.

Age-specific prevalence of Plasmodium falciparum among six populations with limited histories of exposure to endemic malaria.

The age-specific prevalence of Plasmodium falciparum parasitemia among residents of six villages in northeastern Irian Jaya, Indonesia, has been measured for a period of five years. All study subjects were transmigrants from Java living in Irian Jaya for three weeks to 72 months, depending upon the village and point of measurement. Fifteen separate estimates of prevalence were obtained from 4,554 Giemsa-stained thick blood films from 91 to 701 people (mean sample size = 304) among the six villages. The prevalence of parasitemia among people who had lived in Irian Jaya for less than one year did not decrease as a function of age, except in one village at eight months. In contrast, after 16 months to two years or more of residence, the prevalence of parasitemia decreased markedly with increasing age beyond 6-10 or 11-15 years. Social, behavioral, or entomologic characteristics of these populations did not explain the decreasing prevalence of parasitemia with age. An age-dependent naturally acquired protective immunity appeared to develop in all of these villages after 1-2 years of exposure to hyperendemic malaria.

Heightened transmission of stable malaria in an isolated population in the highlands of Irian Jaya, Indonesia.

Malaria at an elevation of 1,500 meters is uncommon and is usually unstable when it occurs. To confirm reports of a recent increase in transmission of stable malaria in the Oksibil Valley, which is at an elevation of 1,250-1,500 meters in the Jayawijaya Mountains of Irian Jaya, Indonesia, five malariometric surveys were conducted in four villages between May 1990 and July 1991. A total of 3,380 blood smears, representative of 1,949 persons, was examined. Prevalence rates over the survey period were consistent in each of the four villages, averaging 10% for infants, 50% for children 1-4 years of age, 35% for those 5-9 years old, 28% for those 10-14 years old, and 16% for adults (greater than 15 years old). The spleen rate for the those less than five years old was 96%, with an average enlarged spleen score of 2.32. Plasmodium falciparum accounted for 55% of the infections in the valley, but P. vivax was the predominant species in those less than 10 years old. In the village of Kutdol at an elevation of 1,500 meters, P. malariae was identified in 43% of the positive smears. Four cases were diagnosed as P. ovale. Infection with P. falciparum without obvious clinical symptoms was common in both adults and children. Entomologic and epidemiologic data suggested that the recent upsurge in transmission coincided with the replacement of traditional village huts with the more modern social housing. This replacement required the extensive construction of drainage ditches, which inadvertently also served as additional vector breeding sites. We suspect that this manipulation of the environment, in an effort to improve the quality of life, created conditions conductive for heightened transmission of stable malaria.

PIP: Malaria at an elevation of 1500 meters is uncommon and is usually unstable when it occurs. To confirm reports of a recent increase in the transmission of stable malaria in the Oksibil Valley, at an elevation of 1250-1500 meters in the Jayawijaya Mountains of Irian Jaya, Indonesia, 5 malariometric surveys were conducted in 4 villages between May 1990 and July 1991. A total of 3380 blood smears from 1949 people was examined. Prevalence rates over the survey period were consistent in each of the 4 villages,with averages of 10% for infants, 50% for children 1-4 years old, 35% for those 5-9 years old, 28% for those 10-14 years old, and 16% for adults (over 15 years of age). The spleen rate for those less than 5 years old was 96%, with an average enlarged spleen score of 2.32. Plasmodium falciparum accounted for 55% of the infections in the valley, but P. vivax was the predominant species in those less than 10 years old. In the village of Kutdol, at an elevation of 1500 meters, P. Malariae was identified in 43% of the positive smears. 4 cases were diagnosed as P. ovale. Infection with P. falciparum without obvious clinical symptoms was common in both adults and children. Entomologic and epidemiologic data suggested that the recent upsurge in transmission coincided with the replacement of traditional village huts with more modern social housing. This replacement required the extensive construction of drainage ditches, which inadvertently also served as additional vector breeding sites. The authors suspect that this manipulation of the environment, while attempting to improve the quality of life, created conditions which were conducive for the increased transmission of stable malaria.

Resistance to chloroquine by Plasmodium vivax in Irian Jaya, Indonesia.

Evidence of emerging resistance to chloroquine by Plasmodium vivax is described from Irian Jaya (Indonesian New Guinea). Sixteen of 24 residents in the village of Arso PIR II taking supervised weekly chloroquine prophylaxis (5 mg base/kg) had asexual parasitemia with P. vivax at least once during eight weeks of surveillance. An American working in the same village developed symptomatic P. vivax parasitemia despite chloroquine prophylaxis. Five days after therapy with 600 mg chloroquine base, the asexual parasitemia in the American increased 40-fold, but cleared after treatment with 1,500 mg chloroquine base. Serum samples were not available from many of the cases, but six local residents and the American had serum levels of chloroquine in excess of the ordinarily suppressive 15 ng/ml at the time of their asexual parasitemias (16-70 ng/ml). The weekly 300 mg base tablet of chloroquine, which has been the standard for prophylaxis against malaria for more than 40 years, was not effective against P. vivax in Arso PIR, Irian Jaya.