What does a single determination of malaria parasite density mean? A longitudinal survey in Mali.

Temporal variations of blood parasite density were evaluated in a longitudinal study of young, asymptomatic men in a village with endemic malaria in Mali (West Africa). Our main intention was to challenge the value of a single measure of parasite density for the diagnosis of malaria, and to define the level of endemicity in any given area. Parasitaemia and body temperature were recorded three times a day in the wet season (in 39 subjects on 12 days) and in the dry season (in 41 subjects on 13 days). Two thousand nine hundred and fifty seven blood smears (98.5% of the expected number) were examined for malaria parasites. We often found 100-fold or greater variations in parasite density within a 6-hour period during individual follow-up. All infected subjects had frequent negative smears. Although fever was most likely to occur in subjects with a maximum parasite density exceeding 10000 parasites/mm3 (P = 0.009), there was no clear relationship between the timing of these two events. Examples of individual profiles for parasite density and fever are presented. These variations (probably due to a 'sequestration-release' mechanism, which remains to be elucidated) lead us to expect a substantial impact on measurements of endemicity when only a single sample is taken. In this study, the percentage of infected individuals varied between 28.9% and 57.9% during the dry season and between 27.5% and 70.7% during the wet season. The highest rates were observed at midday, and there were significant differences between days. Thus, high parasite density sometimes associated with fever can no longer be considered as the gold standard in the diagnosis of malaria. Other approaches, such as decision-making processes involving clinical, biological and ecological variables must be developed, especially in highly endemic areas where Plasmodium infection is the rule rather than the exception and the possible causes of fever are numerous.

A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and omega-3 fatty acids in HIV-infected patients. Swiss HIV Cohort Study.

OBJECTIVE: To evaluate the effects of an oral nutritional supplement enriched with two potentially immunostimulant compounds (arginine and omega-3 fatty acids) on the changes in food intake, body composition, immune parameters and viraemia in HIV-infected outpatients. DESIGN: Six-month prospective randomized double-blind controlled study. SETTING: University hospital outpatient nutrition clinic. PATIENTS: Sixty-four HIV-infected outpatients with CD4 lymphocyte count > or = 10O x 10(6)/l. INTERVENTION: All patients received a daily oral nutritional supplement (606 kcal supplemented with vitamins, trace elements and minerals). In addition, half of the patients were randomized to receive 7.4 g arginine plus 1.7 g omega-3 fatty acids. MAIN OUTCOME MEASURES: Disease progression measured by AIDS-defining events, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors, nutritional status determined by anthropometric, bioelectrical impedance and dietetic assessment. RESULTS: Fifty-five patients completed the protocol. Compliance with and tolerance of oral nutritional supplement during the 6-month period was excellent. In both groups of patients the following were found: total energy intake was transiently increased and then returned to baseline level; nitrogen/energy intake ratio was increased throughout the study; gain of body weight and fat mass were approximately 2 and 1kg, respectively, over 6 months, and were similar in both groups. In addition, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors remained statistically unchanged and were similar in both groups. CONCLUSIONS: Enrichment of an oral nutritive supplement with arginine and omega-3 fatty acids did not improve immunological parameters. However, body weight increased in both groups.

Seasonality and malaria in a west African village: does high parasite density predict fever incidence?

In this cohort study, the authors studied the effect of blood malaria parasite density on fever incidence in children in an endemic area with 9 days' follow-up of 1- to 12-year-old children during two time periods: the end of the dry season (May 1993: n = 783) and the end of the rainy season (October 1993: n = 841) in Bougoula, West Africa (region of Sikasso, Mali). The cumulative incidence of fever (temperature > 38.0 degrees C) was 2.0% in the dry season and 8.2% in the rainy season (p < 0.0001). In the rainy season, the risk of fever was increased in children of ages 1-3 years (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.6-4.1); in those with an initial parasitemia > 15,000/microliter (RR = 2.7, 95% CI 1.4-5.4); in children with an enlarged spleen (RR = 2.0, 95% CI 1.2-3.3); or in those with anemia (hematocrit < 30%: RR = 1.8, 95% CI 1.1-2.9). In the dry season, anemia was the only predictor of fever incidence. In the rainy season, the best predictors of fever were, in order, age (< 4 years), enlarged spleen, and high parasite density. Even in the higher risk groups, the cumulative incidence was < 20%. The authors conclude that most children with high parasite density do not develop fever subsequently. The association between parasite density and fever varies according to age and season. Since even high levels of parasite density do not reliably predict fever incidence, parasite density should be considered as just one of a group of indicators that increase the probability of a fever of malarial origin.

PIP: In a cohort study, the effect of blood malaria parasite density on fever incidence in children was studied in an endemic area with 9 days' follow-up of children aged 1-12 years during two time periods: the end of the dry season (May 1993: n = 783) and the end of the rainy season (October 1993: n = 841) in Bougoula, West Africa (region of Sikasso, Mali). The number of registered children was 928 in the dry season and 998 in the rainy season. Complete follow-up and information were available for 835 children in the dry season and for 964 children in the rainy season. The 9-day cumulative fever incidence (body temperature above 38.0 degrees Celsius) increased from 2.0% in the dry season to 8.2% in the rainy season (p 0.0001). In the rainy season, the risk of fever increased in children aged 1-3 years (relative risk [RR] = 2.5; 95% confidence interval [CI], 1.6-4.1); in those with an initial parasitemia greater than 15,000/mcl (RR = 2.7; 95% CI, 1.4-5.4); in those with an enlarged spleen (RR = 2.0; 95% CI, 1.2-3.3); or in those with anemia (hematocrit 30%: RR = 1.8; 95% CI, 1.1-2.9). In the dry season, anemia (hematocrit 30%) was the only predictor of fever incidence with a cumulative incidence of 10.0%. In nonanemic children, a parasite count of 2000/mcl was the next best predictor. In the rainy season, the best predictors of fever were age (4 years), enlarged spleen, and high parasite density (1/mcl). Even in the higher risk groups, the cumulative incidence was 20%. Most children with high parasite density do not develop fever subsequently. The association between parasite density and fever varies according to age and season. Since even high levels of parasite density do not reliably predict fever incidence, parasite density should be considered not so much a direct marker of an ongoing attack but as just one indicator of the likelihood of a current or imminent attack or even one just passed.

Seasonality, malaria, and impact of prophylaxis in a West African village I. Effect of anemia in pregnancy.

The importance of malaria as a cause of anemia in pregnancy in endemic areas remains controversial. The prevalence of anemia in pregnant women following the dry (May) and the rainy (November) seasons was compared in two successive years in Bougoula village (region of Sikasso, Mali). Phase I (1992) was observational and included 172 pregnant women and 208 controls. In Phase II (1993, 174 pregnant women and 206 controls), malaria prophylaxis with proguanil (200 mg/day) and chloroquine (300 mg/week) was offered to pregnant women. A strong seasonal variation in the prevalence of moderate to severe anemia in pregnant women (hematocrit < 30%) occurred in Phase I (dry season = 8.7%, rainy season = 41.2%). This variation was present only in women of parity lower than five, and paralleled variation in parasitemia. In Phase II, the seasonal variation of anemia was suppressed in women under malaria prophylaxis (presence of antimalarial metabolites in urine), and the overall prevalence of moderate to severe anemia in pregnancy decreased by 55.5% (22.8-74.3%). We conclude that malaria is the major cause of anemia in pregnancy in this region. A high priority should be given to prevention of malaria in pregnancy.

Seasonality, malaria, and impact of prophylaxis in a West African village. II. Effect on birthweight.

The impact of malaria on low birthweight was investigated in Bougoula village (Sikasso region, Mali). In two successive years, pregnant women were followed until delivery. Phase I (1992) was observational, with 135 complete observations. Phase II (1993) included 126 participants, who were offered malaria prophylaxis with proguanil (200 mg/day) and chloroquine (300 mg/week). The results show that 1) infants of first and second pregnancies had lower birth weights (-382.7 +/- 62.6 g; P < 0.0001) compared with higher rank pregnancies; 2) strong seasonal variation in birthweight was observed in Phase I, with an annual cycle, a nadir in January, and an amplitude of 372.4 g (P = 0.0002); 3) parasitemia measured during pregnancy was associated with lower birthweight in infants from first and second pregnancies, but not from higher parity mothers; and 4) malaria prophylaxis taken for 20 weeks or more in Phase II suppressed the seasonal variation of birthweight and the effect of low parity (+423.4 +/- 118.8 g; P = 0.0004). We conclude that malaria in pregnancy has an important negative impact on birthweight in first and second pregnancies. Prophylaxis with proguanil and chloroquine is an effective prophylaxis when taken for 20 weeks or more.