Antibody-mediated growth inhibition of Plasmodium falciparum: relationship to age and protection from parasitemia in Kenyan children and adults

Background

Antibodies that impair Plasmodium falciparum merozoite invasion and intraerythrocytic development are one of several mechanisms that mediate naturally acquired immunity to malaria. Attempts to correlate anti-malaria antibodies with risk of infection and morbidity have yielded inconsistent results. Growth inhibition assays (GIA) offer a convenient method to quantify functional antibody activity against blood stage malaria.

Methods

A treatment-time-to-infection study was conducted over 12-weeks in a malaria holoendemic area of Kenya. Plasma collected from healthy individuals (98 children and 99 adults) before artemether-lumefantrine treatment was tested by GIA in three separate laboratories.

Results

Median GIA levels varied with P. falciparum line (D10, 8.8%; 3D7, 34.9%; FVO, 51.4% inhibition). The magnitude of growth inhibition decreased with age in all P. falciparum lines tested with the highest median levels among children <4 years compared to adults (e.g. 3D7, 45.4% vs. 30.0% respectively, p = 0.0003). Time-to-infection measured by weekly blood smears was significantly associated with level of GIA controlling for age. Upper quartile inhibition activity was associated with less risk of infection compared to individuals with lower levels (e.g. 3D7, hazard ratio = 1.535, 95% CI = 1.012–2.329; p = 0.0438). Various GIA methodologies had little effect on measured parasite growth inhibition.

Conclusion

Plasma antibody-mediated growth inhibition of blood stage P. falciparum decreases with age in residents of a malaria holoendemic area. Growth inhibition assay may be a useful surrogate of protection against infection when outcome is controlled for age.     

Temporal modulation transfer functions in the barn owl (<Emphasis Type="Italic">Tyto alba</Emphasis>)

Barn owls (Tyto alba) have evolved several specializations in their auditory system to achieve the high sensory acuity required for prey capture, including superior processing of interaural time differences and phase coding in the auditory periphery. Here, we tested whether barn owls are capable of high temporal resolution that may be a prerequisite for the accuracy in binaural processing. Temporal resolution was measured psychoacoustically and demonstrated in temporal modulation transfer functions. Four barn owls were trained in an operant task with food reward to detect sinusoidal amplitude modulations within an 800-ms gated white-noise burst or 800-ms periods of modulation in continuous white noise (spectrum levels of -5 dB and 15 dB SPL). Within the range of tested amplitude modulation frequencies from 5 Hz to 1280 Hz, barn owls' detection thresholds were lowest at 10-20 Hz. This sensitivity corresponds to an intensity-difference limen of between 0.9 dB and 1.4 dB. For all conditions, temporal modulation transfer functions showed band-pass characteristics with a high-frequency cutoff in the range of 37 Hz to 92 Hz, corresponding to minimum integration times of 4.3 ms and 1.7 ms, respectively. In summary, these data indicate a temporal resolution in the owl's auditory system that is good, but not unusual, compared to other vertebrates.     

Computer system for assisting with clinical interpretation of tumour marker data.

OBJECTIVE--To design and evaluate a computer advisory system for the treatment of gestational trophoblastic tumour. DESIGN--A comparison of clinicians'' treatment decisions with those of the computer system. Two datasets were used: one to calibrate the system and one to independently evaluate it. SETTING--Department of medical oncology. PATIENTS--Computerised records of 290 patients with low risk gestational trophoblastic tumour for whom the advisory system could predict the adequacy of treatment. The calibration set comprised patients admitted during 1979-86(227) and the test set patients during 1986-89(63). MAIN OUTCOME MEASURES--The system''s accuracy in predicting need to change treatment compared with clinicians'' actions. The mean time faster that the system was in predicting the need to change treatment. RESULTS--On the calibration dataset the system was 94% (164/174) accurate in predicting patients whose treatment was adequate, recommending change when none occurred in only 10 (6%) patients. In patients whose treatment was changed the system recommended change earlier than clinicians in 39/53 cases (74%), with a mean time advantage of 14.9 (SE 2.02) days. On the test dataset the system had an accuracy of 91% (31/34) in predicting treatment adequacy and a false positive rate of 9% (3/34). The system recommended change earlier than clinicians in 22/29 cases (76%), with a mean time advantage of 12.5 (2.22) days. CONCLUSIONS--The computer advisory system could improve patient management by reducing the time spent receiving ineffective treatment. This has implications for both patient time and clinical costs.     

Preregistration house officers in eight English regions: survey of quality of training.

OBJECTIVE--To assess the quality of preregistration house officer training in eight English regions. DESIGN--Postal questionnaire. SETTING--Thames, East Anglian, Mersey, Northern, and Wessex regions. PARTICIPANTS--1670 preregistration house officers. MAIN OUTCOME MEASURES--Education, hours of work, workload, conditions of work, and attitudes to job and medicine as a career. RESULTS--Response rate was 69% (1146 replies). Most house officers had attended induction courses (1036/1129 (92%)); 74% (757/1024) found them satisfactory. The proportions who had never received adequate guidance on how to break bad news and how to control pain were 59% (670/1135) and 56% (634/1136) respectively. There was much variation between regions. Overall, 65% (736/1138) reported confidence in performing cardiopulmonary resuscitation. Most respondents (95% (1089/1142)) worked an on call rota, 3% (36) a partial shift, and 0.6% (seven) a full shift; 19% (202) were on duty for average weekly hours that exceeded the targets for 1 April 1993. House officers had a median of 20 patients under their care and clerked a median of 10 emergency cases, six routine cases, and two day cases a week. Over half (690/1128 (61%)) could not obtain hot food after 8 pm, 20% (223/1095) did not always have clean sheets available in their on call room, and 45% (462/1036) did not consider the protection of staff against violence to be adequate at their hospital. The most important problems with the preregistration year were inappropriate or non-medical tasks (ranked first by 360 respondents), hours of work (359), and pay for out of hours work (167). Overall 57% (646/1125) would encourage a friend to apply for their post, but only 24% (266/1112) would encourage a friend to take up medicine and 44% (494/1112) would discourage the idea. CONCLUSIONS--House officers'' training is deficient in important respects, with inappropriate tasks and heavy clinical workloads impeding the provision of proper education.