Biomedical subjects

A J Oloo

Publications and source records attributed to A J Oloo.

At least 37 records · Page 2Linked to original sources

PubMed1998

Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection.

A fever case management (CM) approach using sulfadoxine-pyrimethamine (SP) was compared with two presumptive intertmittent SP treatment regimens in the second and third trimesters in pregnant primigravidae and secundigravidae in an area of intense Plasmodium falciparum malaria transmission in western Kenya. The investigation evaluated efficacy of the antimalarial regimens for prevention of placental malaria and examined the effect of human immunodeficiency virus (HIV) infection on antimalarial drug efficacy and adverse drug reactions. Twenty-seven percent (93 of 343) of pregnant women in the CM group had placental malaria compared with 12% (38 of 330; P < 0.001) of women who received two doses of SP and compared with 9% (28 of 316; P < 0.001) of women who received monthly SP. Fourteen percent (49 of 341) of women in the CM group delivered low birth weight (LBW) infants compared with 8% (27 of 325; P=0.118) of women who received two doses of SP and compared with 8% (26 of 331; P=0.078) of women who received monthly SP. Seven percent (7 of 99) of the HIV-negative women on the two-dose SP regimen had placental malaria compared with 25% (10 of 39; P=0.007) of HIV-positive women on the same regimen; the rate of placental malaria in HIV-positive women was reduced to 7% (2 of 28; P=-0.051) for women on the monthly SP regimen. Less than 2% of women reported adverse drug reactions, with no statistically significant differences between HIV-positive and HIV-negative women. Intermittent treatment with SP is safe and efficacious for the prevention of placental malaria in pregnant primigravidae and secundigravidae in sub-Saharan Africa. While a two-dose SP regimen may be effective in areas with low HIV seroprevalence, administration of SP monthly during the second and third trimesters of pregnancy should be considered in areas of high HIV seroprevalence to prevent the effects of maternal malaria on the newborn.

Adolescent↗

PubMed1997

Dose- and time-dependent relations between infective Anopheles inoculation and outcomes of Plasmodium falciparum parasitemia among children in western Kenya.

Blood-stage level Plasmodium falciparum infection (parasitemia density) is generally elevated prior to, or at the time of, clinical presentation of severe pediatric malaria episodes. Intensity of exposure to infective Anopheles mosquito bites is a suspected determinant of higher density parasitemia. Analyses of entomologic and parasitologic data collected in 1986-1987 were conducted to investigate whether the dose of infective bites predicted the incidence or degree of P. falciparum parasitemia in Kenyan children < 6 years old. At 21 consecutive 30-day intervals, a new cohort (n approximately 50 each) was enrolled, cured of malaria parasites, and monitored over 84 days for recurrent parasitemia. Outcomes included time to parasitemia, time to parasitemia > or = 5,000/microliter, and parasitemia density. Ecologic and individual-level analyses were conducted. The mean infective bite exposure experienced by each cohort was significantly associated with the incidence of parasitemia (age-adjusted r2 = 0.38, p = 0.022) and more strongly associated with the incidence of parasitemia > or = 5,000/microliter (age-adjusted r2 = 0.72, p < 0.001). The infective bite dose, analyzed as a time-dependent covariate, was associated with a 2.8 times higher rate of parasitemia > or = 5,000/microliter among children exposed to > or = 1 infective bite per day as compared with the referent (rate ratio (RR) = 2.82, 95% confidence interval (CI) 2.24-3.56). Cumulative infective bite exposure, exposure duration, and age were significant predictors of recurrent parasitemia density in multiple linear regression analyses. The results support the contention that reductions in P. falciparum transmission intensity, in the absence of complete elimination, will reduce higher level parasitemia among African children.

Animals↗

PubMed1997

Cytotoxic T cell reactivity and HLA-B35 binding of the variant Plasmodium falciparum circumsporozoite protein CD8+ CTL epitope in naturally exposed Kenyan adults.

In this study, we have investigated the extent of natural polymorphism in the CD8+ cytotoxic T lymphocyte (CTL) determinant (amino acids 368-390) of circumsporozoite (CS) protein of Plasmodium falciparum field isolates from a holoendemic region of Kenya, and determined how this variation affects the CTL reactivities in clinically immune adults and binding specificities to human histocompatibility leukocyte antigen (HLA)-B35. Among the eight variant sequences that were found in this region, four were new and not seen in parasites from other geographical regions. When synthetic peptides corresponding to the eight variants were used to test the presence of CTL response in different donors, a different spectrum of CTL reactivity to these variants was noticed. While CTL from some donors recognized the P1 sequence (the most prevalent type of sequence) but not P8 (another major variant), other donors showed a reverse pattern of reactivity. Although none of the donors was able to recognize all the variants, CTL responses to all the eight variant sequences were found in this population. An octamer peptide with P1 sequence KPKDELDY in this polymorphic determinant was known to bind HLA-B35. When we tested the effect of natural variation in this octamer sequence on HLA-B35 binding, it became evident that SP13 with D --> N substitution retained its binding specificity to HLA-B35. On the other hand, the SP12 octamer sequence which had two substitutions did not bind HLA-B35. The most interesting finding was the observation that a D --> G substitution at position 374 rescued the binding ability of SP14, which otherwise could not bind to this HLA molecule due to E --> Q amino acid substitution at position 372. To our knowledge, this is the first demonstration showing that a natural polymorphism can rescue the binding specificity to an HLA-class I molecule that was lost due to another natural amino acid substitution. Altogether, these results demonstrate that natural polymorphism in the CS protein affects both the CTL reactivity and the ability to bind to HLA-B35.

Adult↗

PubMed1997

Plasmodium falciparum gametocytemia in Kenyan children: associations among age, intensity of exposure to transmission, and prevalence and density of subsequent gametocytemia.

Recently, an association was described between the density of Plasmodium falciparum asexual parasitemia in Kenyan children and the entomologic inoculation rate (EIR) measured prior to measurement of asexual parasitemia. This study examined whether transmission pressure, as represented by the EIR, was associated with the prevalence or density of gametocytemia in Kenyan children. Each month for 19 months, a cohort of approximately 50 children was given a radical cure and enrolled in the study. Blood films were taken on days 0, 7, and 14. The EIR was calculated for the 28-day period ending 14 days prior to enrollment: the relationship between blood film data from day 7 and exposure variables was explored. We found that younger children were more likely to be gametocytemic than older children and, if gametocytemic, were more likely to have a dense gametocytemia. There was an inverse relationship between the number of infective bites per night received and prevalence but not density of gametocytemia, even after age adjustment. Concordance of gametocytemia prevalence on days 0 (64%), 7 (66%), and 14 (52%) was poor; 84% of the children were positive on at least one day. This indicates that in many subjects the detectable gametocytemia varied over the 14 days. Under these holoendemic transmission conditions, the EIR is inversely correlated with prevalence of gametocytemia, and point measurements of gametocytemia by conventional microscopy underestimate the number of infective donor hosts.

Age Factors↗

PubMed1997

Evaluation of an algorithm for integrated management of childhood illness in an area of Kenya with high malaria transmission.

In 1993, the World Health Organization completed the development of a draft algorithm for the integrated management of childhood illness (IMCI), which deals with acute respiratory infections, diarrhoea, malaria, measles, ear infections, malnutrition, and immunization status. The present study compares the performance of a minimally trained health worker to make a correct diagnosis using the draft IMCI algorithm with that of a fully trained paediatrician who had laboratory and radiological support. During the 14-month study period, 1795 children aged between 2 months and 5 years were enrolled from the outpatient paediatric clinic of Siaya District Hospital in western Kenya; 48% were female and the median age was 13 months. Fever, cough and diarrhoea were the most common chief complaints presented by 907 (51%), 395 (22%), and 199 (11%) of the children, respectively; 86% of the chief complaints were directly addressed by the IMCI algorithm. A total of 1210 children (67%) had Plasmodium falciparum infection and 1432 (80%) met the WHO definition for anaemia (haemoglobin < 11 g/dl). The sensitivities and specificities for classification of illness by the health worker using the IMCI algorithm compared to diagnosis by the physician were: pneumonia (97% sensitivity, 49% specificity); dehydration in children with diarrhoea (51%, 98%); malaria (100%, 0%); ear problem (98%, 2%); nutritional status (96%, 66%); and need for referral (42%, 94%). Detection of fever by laying a hand on the forehead was both sensitive and specific (91%, 77%). There was substantial clinical overlap between pneumonia and malaria (n = 895), and between malaria and malnutrition (n = 811). Based on the initial analysis of these data, some changes were made in the IMCI algorithm. This study provides important technical validation of the IMCI algorithm, but the performance of health workers should be monitored during the early part of their IMCI training.

Algorithms↗

PubMed1997

Assessment of potential indicators for protein-energy malnutrition in the algorithm for integrated management of childhood illness.

Potential indicators were assessed for the two classifications of protein-energy malnutrition in the guidelines for integrated management of childhood illness: severe malnutrition, which requires immediate referral to hospital, and very low weight, which calls for feeding assessment, nutritional counselling and follow-up. Children aged < 2 years require feeding assessment and counselling as a preventive intervention. For severe malnutrition, we examined 1202 children admitted to a Kenyan hospital for any association of the indicators with mortality within one month. Bipedal oedema indicating kwashiorkor, and two marasmus indicators (visible severe wasting and weight-for-height (WFH) Z-score of < -3) were associated with a significantly increased mortality risk (odds ratios, 3.1-3.9). Very low weight-for-age (WFA) (Z-score of < -4.4) was not associated with an increased risk of mortality. Because first-level health facilities generally lack length-boards, bipedal oedema and visible severe wasting were chosen as indicators of severe malnutrition. To assess potential WFA thresholds for the very low weight classification, our primary source of data came from 1785 Kenyan outpatient children, but we also examined data from surveys in Nepal, Bolivia, and Togo. We examined the performance of WFA at various thresholds to identify children with low WFH and, for children aged < or = 2 years, low height-for-age (HFA). Use of a WFA threshold Z-score of < -2 identified a considerable proportion of children (from 13% in Bolivia to 68% in Nepal) which, in most settings, would pose an enormous burden on the health facility. Among ill children in Kenya, a threshold WFA Z-score of < -3 had a sensitivity of 89-100% to detect children with WFH Z-scores of < -3, and, with an identification rate of 9%, would avoid overburdening the clinics. Potential modifications include use of a more restrictive cut-off in countries with high rates of stunting, or the elimination of the WFA screen in order to concentrate efforts on intervention for all children below the 2-year age cut-off. Key issues in every country include the capacity to provide counselling for many children and linkage to nutritional improvement programmes in the community.

Age Factors↗

PubMed1996

Plasmodium falciparum circumsporozoite vaccine immunogenicity and efficacy trial with natural challenge quantitation in an area of endemic human malaria of Kenya.

It has been hypothesized that antibody induced by Plasmodium falciparum circumsporozoite protein vaccine would be effective against endemic human malaria. In a malaria endemic region of Kenya, 76 volunteers, in 38 pairs sleeping adjacently, were immunized with subunit circumsporozoite protein Asn-Ala-Asn-Pro tetrapeptide repeat-pseudomonas toxin A, or hepatitis B vaccine. After quinine and doxcycycline, volunteers were followed for illness daily, parasitemia weekly, antibody, T-lymphocyte responses, and treated if indicated. Anopheles mosquitoes resting in houses were collected, and tested for P. falciparum antigen, or dissected for sporozoites and tested for blood meal ABO type and P. falciparum antigen. Vaccine was safe, with side-effects similar in both groups, and immunogenic, engendering IgG antibody as high as 600 micrograms ml-1, but did not increase the proportion of volunteers with T-lymphocyte responses. Estimation of P. falciparum challenge averaged 0.194 potentially infective Anopheles bites/volunteer/ day. Mosquito blood meals showed no difference in biting intensity between vaccine and control groups. Both groups had similar malaria-free survival curves, cumulative positive blood slides, cumulative parasites mm-3, and numbers of parasites mm-3 on first positive blood slide, during three post-vaccination observation periods. Every volunteer had P. falciparum parastemia at least once. Vaccinees had 82% and controls 89% incidences of symptomatic parasitemia (P = 0.514, efficacy 9%, statistical power 95% probability of efficacy < 50%). Vaccine-induced anti-sporozoite antibody was not protective in this study. Within designed statistical precisions the present study is in agreement with efficacy studies in Colombia, Venezuela and Tanzania.

Animals↗

PubMed1996

Field evaluation of a polymerase chain reaction-based nonisotopic liquid hybridization assay for malaria diagnosis.

In a blind field evaluation of a nonisotopic liquid hybridization assay for detection of malaria parasites, 100 blood samples were tested from an area in which malaria is endemic; light microscopy was used as the reference test. Sensitivity, specificity, and positive and negative predictive values of the hybridization assay were 100%. One sample that was microscopy-negative and hybridization-positive was positive when reexamined. Another sample that was microscopy-positive and hybridization-negative was negative at reexamination. The detection limit of the test was > or = 0.0005% parasitemia. Four samples with mixed infections were misdiagnosed by microscopy as single-species infections. Four samples diagnosed as mixed infections by microscopy and single infection by the hybridization test had no evidence of a second Plasmodium species upon reexamination. The polymerase chain-reaction-based nonisotopic liquid hybridization assay was better than conventional light microscopy in detecting low-grade parasite infection and offers an exceptional advantage for detecting mixed infections.

Adolescent↗

PubMed1996

Identification of T-cell determinants in natural immune responses to the Plasmodium falciparum apical membrane antigen (AMA-1) in an adult population exposed to malaria.

AMA-1 of Plasmodium falciparum is a promising candidate antigen in malaria vaccine development. In this study, we have mapped the immunodominant T-cell determinants in this antigen by using synthetic peptides. From the amphipathic scores, 17 putative T-cell determinants were identified. Nine of the 17 peptides complementary to the putative T-cell determinants induced proliferation of peripheral blood mononuclear cells (PBMC) from Kenyan residents who had lifelong exposure to malaria; none of these peptides induced proliferation of PBMC from donors who were not previously exposed to malaria. This indicates that AMA-1 peptides were stimulating T cells that were previously primed by prior exposure to P. falciparum. Many positive responders showed reactivity to more than one peptide, and some of the potent proliferative T epitopes were found to be localized in the highly conserved regions of AMA-1, suggesting that it may be possible to induce T-cell memory that can recognize different variant forms of the parasite. This information on the natural immune responses against the AMA-1 vaccine antigen in clinically immune adults will be helpful in the development of an AMA-1 antigen-based malaria vaccine and may also guide testing of AMA-1-based vaccine formulations.

Adult↗

PubMed1996

Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1.

We have characterized the natural immune responses to the 19-kDa domain of merozoite surface protein 1 in individuals from an area of western Kenya in which malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell proliferative responses in individuals older than 15 years and the profile of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35% of the individuals responded to the E-KNG and E-TSR constructs, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant antigens was observed in different individuals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antibody, IgG1 and IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that IgG1 antibody response may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Furthermore, we observed that although the natural antibodies cross-reacted with all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second epidermal growth factor domain (KNG and TSR) of the antigen.

Adolescent↗

PubMed1996

Some emerging issues on the malaria problem in Kenya.

Malaria in Kenya has been characterised by marked variability in its epidemiology, partly reflecting the obstacles and progress made in the control strategies. The impact of anti-vector activities in the 1970s and before have been observed for variable lengths of time afterwards. Malaria has re-emerged in areas previously with little or no transmission. The recovery of infective Anopheles gambiae vector in higher altitudes affirms the potential for transmission in areas where epidemics have been known to occur. Morbidity and mortality patterns in the otherwise endemic lowlands have become increasingly severe, an observation which would be attributed to the increasing inefficacy of chloroquine. Efforts to promote personal protection suffer substantial setbacks in sustainability inspite of apparent acceptability. There are indications that the mosquito vector susceptibility to permethrin and other insecticides will now require continual monitoring in order to detect development of significant resistance. In this communication, we review some emergent issues in malaria transmission in Kenya and the potential for control as adduced from historical and contemporary perspectives.

Altitude↗

PubMed1995

Daily primaquine is effective for prophylaxis against falciparum malaria in Kenya: comparison with mefloquine, doxycycline, and chloroquine plus proguanil.

Primaquine was tested as a prophylactic drug against Plasmodium falciparum in a region in western Kenya in which malaria is holoendemic. Children 9-14 years old were randomized to receive regimens of daily primaquine, daily doxycycline, daily proguanil plus weekly chloroquine, daily vitamin plus weekly mefloquine, or daily vitamin alone. Primaquine, doxycycline, and mefloquine were equally effective in preventing both symptomatic and asymptomatic malarial infections. Chloroquine plus proguanil was the least effective regimen. There was no toxicity from daily primaquine during the 11 weeks of the study. Findings show that primaquine can be successfully used as a causal prophylactic regimen against falciparum malaria in western Kenya; chloroquine plus proguanil was not as efficacious as the three other preventive regimens; most Kenyan children receiving standard doses of mefloquine and doxycycline had lower than expected serum trough drug levels; and some volunteers with adequate mefloquine or doxycycline levels at trough developed asymptomatic parasitemias and clinical malaria.

Adolescent↗

PubMed1995

Impact of transmission intensity and age on Plasmodium falciparum density and associated fever: implications for malaria vaccine trial design.

To facilitate design of vaccine trials, malaria was studied in 6-month- to 6-year-old Kenyans during high (HI) and low intensity transmission seasons. During 84 days after cure, exposure to infected mosquitoes was 9-fold greater in the HI group, yet incidence of P. falciparum infection was increased only 2-fold, with no age effect. The density of recurrent P. falciparum was 14-fold greater in the HI group, and there was a striking association between age and parasitemia > or = 5000/microL. Fever was the only clinical manifestation attributable to parasitemia and only when the parasite density was > or = 5000/microL. Sixty-four percent of children with > or = 20,000 parasites/microL versus 10% with 1-4999/microL were febrile when parasitemic. Recurrent P. falciparum infection as a vaccine trial end point can be studied year-round among children < or = 6 years [corrected] in western Kenya. However, high-grade parasitemia (> or = 5000 or 20,000/microL) with or without elevated temperature will be optimally studied in the high transmission season among children < 2 years.

Age Factors↗

PubMed1995

Self-treatment of malaria in a rural area of western Kenya.

Reported are the results of a study of residents' knowledge about malaria and antimalarial drugs and of their treatment-seeking behaviour in a rural area of western Kenya. The study subjects were generally well-informed about the symptoms of the disease. Malaria was perceived as a relatively mild illness, much less severe than acquired immunodeficiency syndrome (AIDS), measles, difficulty in breathing, and diarrhoea. Self-treatment was extremely common: of 138 episodes of febrile illness, 60% were treated at home with herbal remedies or medicines purchased at local shops, and only 18% received treatment at a health centre or hospital; no treatment was sought by the remainder. Commercially available chloroquine preparations were perceived as more effective than either antipyretics or herbal remedies for the treatment of malaria, and injections were regarded as more effective than oral medications. 4-Amino-quinolines were used to treat 58% of febrile illnesses but in only 12% of the cases was a curative dose of > or = 25 mg/kg body weight employed. Even attendance at a health centre did not ensure adequate treatment because of the common practice of sharing medication among family members. Greatly increased attention should be paid to the role of home treatment of malaria when policies are being developed for the management of febrile illnesses in sub-Saharan Africa.

Adolescent↗

PubMed1995

Efficacy of halofantrine in the treatment of uncomplicated falciparum malaria.

In the last decade, Plasmodium falciparum resistance to a number of commonly used anti-malarials especially chloroquine, has increased considerably. Newer anti-malarial drugs are therefore being aggressively evaluated as alternatives. A randomized double-blind controlled trial was therefore undertaken, to compare the efficacy of halofantrine to that of metakelfin, in the treatment of moderately severe infections of Plasmodium falciparum in an endemic malaria area in Kenya. Three hundred and thirty five subjects with laboratory confirmed malaria were recruited and randomized to receive treatment with either halofantrine (171 subjects) or metakelfin (164 subjects). Two thirds (66%) of the study subjects were under the age of five years, and were therefore considered to have minimal immunity. All study subjects were initially admitted to hospital for three days and then followed up as out-patients on days 7, 14, 21, and 28. The level of parasitaemia, the presence of fever and the occurrence of adverse effects were evaluated. Halofantrine was found to be comparable to metakelfin in terms of resolution of fever (mean time 45 and 51 hours respectively). No major adverse side effects were observed. Halofantrine is a viable drug in the treatment of uncomplicated P. falciparum malaria.

Adolescent↗

PubMed1994

Diagnosis of malaria by detection of Plasmodium falciparum HRP-2 antigen with a rapid dipstick antigen-capture assay.

Two field studies in Kenya and an experimental challenge study in the USA were done to assess the accuracy of a dipstick antigen-capture assay based on qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) in peripheral blood for diagnosis of P falciparum infection. In these studies, the assay was 96.5-100% sensitive for detection of greater than 60 P falciparum asexual parasites/microL blood, 70-81% sensitive for 11-60 parasites/microL blood, and 11-67% sensitive for 10 parasites or less/microL blood. Specificity was 95% (95% CI 85-105%; n = 20) among naive American volunteers, 98% (96-101%; n = 112) among volunteers exposed to the bite of P falciparum-infected mosquitoes, and 88% (84-92%; n = 285) among Kenyans living in an area with holoendemic malaria. Our results also indicated that PfHRP-2 antigen was not detectable in blood 6 days after initiation of curative chemotherapy, and suggest that such circulating antigens rarely lead to false-positive tests. The dipstick assay's sensitivity, specificity, simplicity, and speed may make it an important tool in the battle against malaria.

Adolescent↗

PubMed1994

Evaluation of the QBC method to detect malaria infections in field surveys.

The conventional peripheral blood film method used to diagnose malaria is characterized by low sensitivity in scanty parasitaemia and can be time consuming when required to rule out infection. The Quantitative Buffy Coat (QBC) method has been proposed to be quicker and more sensitive. We conducted a malaria survey in April 1992 among school-children in Kisumu (holoendemic) and Webuye (hypoendemic) areas of Western Kenya. Peripheral blood samples were examined by thick blood smear (TBS) stained with Giemsa solution, and by the QBC method. A total of 360 paired samples were analyzed. There were 175 (49%) positive TBS and 201 (56%) positive QBC. Of the 185 TBS classified as negative, 30 (16%) were positive by QBC. When parasite density by TBS was > or = 100/300 WBCs, the sensitivity of QBC was 100%. Overall sensitivity for QBC was 98%, with a specificity of 84%. Negative predictive value for the QBC was 98%, and had a calculated accuracy of 92%. It took an average of 44 minutes to process a TBS and a further average of 2.6 minutes to examine a negative TBS. For the QBC the mean time to process and to examine was 7.09 and 1.04 minutes respectively. We conclude that the QBC is quicker, with high sensitivity, and will prove useful in clinical and epidemiological screening, especially when parasitaemia is low.

Azure Stains↗

PubMed1994

Predicting outcome in malaria: correlation between rate of exposure to infected mosquitoes and level of Plasmodium falciparum parasitemia.

The level of Plasmodium falciparum parasitemia at clinical presentation has repeatedly been shown to correlate with severity of disease. Using data collected in western Kenya over 21 months, we examined associations between exposure variables, especially exposure to infective mosquitoes, and prevalence and density of P. falciparum parasitemia among 1,007 children six months to six years of age. The prevalence of P falciparum infection was similar at all exposure levels, but there was a correlation between exposure to sporozoite-infected mosquitoes over the previous 28-day period, and geometric mean parasite density of each cohort (Spearman rank coefficient = 0.724, P = 0.002). The relative odds of having a parasite density > or = 5,000/microliters was increased almost two-fold among individuals exposed to more than 10 infective bites during the prior 28-day period. Children enrolled during the highest incidence period were 80% more likely to have a density > or = 5,000/microliters relative to individuals enrolled during periods of lower incidence. The data suggest that measures, such as malaria vaccines, that reduce parasite densities by limiting numbers of sporozoites reaching the liver, or merozoites released from the liver, will reduce malaria-associated morbidity and mortality, even when they do not prevent all infections.

Age Factors↗