Preliminary evaluation of dual-energy CT to quantitatively assess bone marrow edema in patients with diabetic foot ulcers and suspected osteomyelitis.

OBJECTIVES: The purpose of this study is to evaluate the value of dual-energy CT (DECT) with virtual non-calcium (VNCa) in quantitatively assessing the presence of bone marrow edema (BME) in patients with diabetic foot ulcers and suspected osteomyelitis. METHODS: Patients with a diabetic foot ulcer and suspected osteomyelitis that underwent DECT (80 kVp/Sn150 kVp) with VNCa were retrospectively included. Two observers independently measured CT values of the bone adjacent to the ulcer and a reference bone not related to the ulcer. The patients were divided into two clinical groups, osteomyelitis or no-osteomyelitis, based on the final diagnosis by the treating physicians. RESULTS: A total of 56 foot ulcers were identified of which 23 were included in the osteomyelitis group. The mean CT value at the ulcer location was significantly higher in the osteomyelitis group (- 17.23 ± 34.96 HU) compared to the no-osteomyelitis group (- 69.34 ± 49.40 HU; p < 0.001). Within the osteomyelitis group, the difference between affected bone and reference bone was statistically significant (p < 0.001), which was not the case in the group without osteomyelitis (p = 0.052). The observer agreement was good for affected bone measurements (ICC = 0.858) and moderate for reference bone measurements (ICC = 0.675). With a cut-off value of - 40.1 HU, sensitivity was 87.0%, specificity was 72.7%, PPV was 69.0%, and NPV was 88.9%. CONCLUSION: DECT with VNCa has a potential value for quantitatively assessing the presence of BME in patients with diabetic foot ulcers and suspected osteomyelitis. KEY POINTS: • Dual-energy CT (DECT) with virtual non-calcium (VNCa) is promising for detecting bone marrow edema in the case of diabetic foot ulcers with suspected osteomyelitis. • DECT with VNCa has the potential to become a more practical alternative to MRI in assessing the presence of bone marrow edema in suspected osteomyelitis when radiographs are not sufficient to form a diagnosis.

Albumin, a marker for post-operative myocardial damage in cardiac surgery.

PURPOSE: Low serum albumin (SA) is a prognostic factor for poor outcome after cardiac surgery. The aim of this study was to estimate the association between pre-operative SA, early post-operative SA and postoperative myocardial injury. METHODS: This single center cohort study included adult patients undergoing cardiac surgery during 4 consecutive years. Postoperative myocardial damage was defined by calculating the area under the curve (AUC) of troponin (Tn) values during the first 72 h after surgery and its association with SA analyzed using linear regression and with multivariable linear regression to account for patient related and procedural confounders. The association between SA and the secondary outcomes (peri-operative myocardial infarction [PMI], requiring ventilation >24 h, rhythm disturbances, 30-day mortality) was studied using (multivariable) log binomial regression analysis. RESULTS: In total 2757 patients were included. The mean pre-operative SA was 29 ±â€¯13 g/l and the mean post-operative SA was 26 ±â€¯6 g/l. Post-operative SA levels (on average 26 min after surgery) were inversely associated with postoperative myocardial damage in both univariable analysis (regression coefficient - 0.019, 95%CI -0.022/-0.015, p < 0.005) and after adjustment for patient related and surgical confounders (regression coefficient - 0.014 [95% CI -0.020/-0.008], p < 0.0005). CONCLUSIONS: Post-operative albumin levels were significantly correlated with the amount of postoperative myocardial damage in patients undergoing cardiac surgery independent of typical confounders.

Acute Kidney Injury Classification Underestimates Long-Term Mortality After Cardiac Valve Operations.

BACKGROUND: Perioperative acute kidney injury (AKI) is an important predictor of long-term all-cause mortality after coronary artery bypass (CABG). However, the effect of AKI on long-term mortality after cardiac valve operations is hitherto undocumented. METHODS: Perioperative renal injury and long-term all-cause mortality after valve operations were studied in a prospective cohort of patients undergoing solitary valve operations (n = 2,806) or valve operations combined with CABG (n = 1,260) with up to 18 years of follow-up. Postoperative serum creatinine increase was classified according to AKI staging 0 to 3. Patients undergoing solitary CABG (n = 4,938) with cardiopulmonary bypass served as reference. RESULTS: In both valve and valve+CABG operations, postoperative renal injury of AKI stage 1 or higher was progressively associated with an increase in long-term mortality (hazard ratio [HR], 2.27, p < 0.05 for valve; HR, 1.65, p < 0.05 for valve+CABG; HR, 1.56, p < 0.05 for CABG). Notably, the mortality risk increased already substantially at serum creatinine increases of 10% to 25%-that is, far below the threshold for AKI stage 1 after valve operations (HR, 1.39, p < 0.05), but not after valve operations combined with CABG or CABG only. CONCLUSIONS: An increase in serum creatinine by more than 10% during the first week after valve operation is associated with an increased risk for long-term mortality after cardiac valve operation. Thus, AKI classification clearly underestimates long-term mortality risk in patients undergoing valve operations.

Comparing peri-operative complications of paediatric and adult anaesthesia: A retrospective cohort study of 81 267 cases.

BACKGROUND: Comparisons of peri-operative complications associated with paediatric (≤16 years) and adult anaesthesia are poorly available, especially in which cardiac surgery, organ transplantation and neurosurgery are involved. OBJECTIVE: The aim of this study was to evaluate the nature and incidence of peri-operative complications that might be due to anaesthesia and to identify independent risk factors for complications in children and adults, including those undergoing cardiac surgery, organ transplantation and neurosurgery. DESIGN: Retrospective cohort study. SETTING: The study was performed at the University Medical Centre Groningen in the 4 years between 1 January 2010 and the 31 December 2013. MAIN OUTCOME MEASURES: Complications and their severity were graded according to the standard complication score (20 items) of the Dutch Society of Anaesthesia. Univariate and multivariate regression analysis was used to identify independent risk factors for the reported complications. RESULTS: A total of 81 267 anaesthetic cases were included. In the paediatric cohort, there were 410 (2.9%) complications and 1675 (2.5%) in the adults. In both cohorts age, American Society of Anaesthesiologists classification and emergency treatment were independent risk factors for complications. With respect to age, infants less than 1 year were at the highest risk, whereas in the adult cohort, increased age was related to a greater number of complications. The incidences of the specific complications were different between both cohorts. Upper airway obstruction was more frequently observed in paediatric patients (26%), whereas in the adults, complications with the highest incidence concerned conversion of regional-to-general anaesthesia (25%) and hypotension (17%). CONCLUSION: Risk factors for all peri-operative complications were similar for paediatric and adult anaesthesia. However, the incidence of specific complications differed between both age categories.

The living company.

What can explain the longevity gap between a company that survives for centuries--the Swedish company Stora, for example, which is more than 700 years old--and the average corporation, which does not last 20 years? A team at Royal Dutch/Shell Group explored that question. Arie de Geus, a retired Shell executive, writes about the team's findings and describes what he calls living companies-organizations that have beaten the high mortality rate of the average corporation. Many companies die young, de Geus argues, because their policies and practices are based too heavily on the thinking and language of economics. Their managers focus on producing goods and services and forget that the organization is a community of human beings that is in business--any business--to stay alive. In contrast, managers of living companies consider themselves to be stewards of a long-standing enterprise. Their priorities reflect their commitment to the organization's long-term survival in an unpredictable world. Like careful gardeners, they encourage growth and renewal without endangering the plant they are tending. They value profits the same way most people value oxygen: as necessary for life but not the purpose of it. They scuttle assets when necessary to make a dramatic change in the business portfolio. And they constantly search for new ideas. These managers also focus on developing people. They create opportunities for employees to learn from one another. Such organizations are suited for survival in a world in which success depends on the ability to learn, to adapt, and to evolve.

Comparison of three malaria chemoprophylactic regimens in residents in east, central and southern Africa. A prospective, randomized multicentre trial in The Netherlands.

There is much confusion about the most effective malaria chemoprophylactic regimen for travellers to chloroquine-resistant areas. For residents, the problem is even more confused. A prospective, multicentre trial was performed between 1987 and 1989 to assess the efficacy of three different malaria chemoprophylactic regimens (chloroquine 300 mg weekly combined with proguanil 100 mg daily, chloroquine 300 mg weekly combined with proguanil 200 mg daily and proguanil 200 mg daily only) in Dutch expatriates, who were departing for a stay of more than one year in East, Central or Southern Africa. Prophylaxis failures (defined as Plasmodium falciparum present in the blood film) were distinguished from failures of compliance by measuring whole-blood drug levels, taken at the same time as the blood slide and sent as filterpaper blood spots. The data of 200 expatriates could be analysed; the overall response rate was 52%. Twenty-six (13%) suffered from a fever; in two of them the blood slide contained P. falciparum. One subject took chloroquine 300 mg weekly with proguanil 200 mg daily, the other 200 mg proguanil daily. Assessment of compliance was possible in 10 of the 26 subjects with a fever; five (50%) were below and five (50%) were above the limit of 0.19 mumol/l. Due to the low incidence of prophylaxis failures, calculation of risks is unreliable. There were strong indications that compliance decreased with time. The ultimate cooperation needed for confirmation of prophylaxis failures and breakthroughs failed. Several factors which could have contributed to this lack of cooperation are discussed.

Falciparum malaria, imported into The Netherlands, 1979-1988. II. Clinical features.

To study the clinical features in patients with falciparum malaria and the influence of chloroquine chemoprophylaxis on these features, a prospective study was carried out of all non-immune patients with falciparum malaria between 1979 and 1988. Three hundred and sixty-one consecutive non-immune patients with falciparum malaria who were seen at the outpatient-department for Tropical Diseases, Royal Tropical Institute, and Division of Infectious Diseases and Tropical Medicine of the University Hospitals of the University of Amsterdam, The Netherlands. Compliance with the recommended malaria prophylaxis was claimed by 47% (168/361); 24% (86/361) had not taken any chemoprophylaxis. The first group had a milder illness, less often parasitaemia > or = 1% and suffered less from complications. Comparison of the clinical features in patients who did not take prophylaxis and those who, during recommended prophylaxis, appeared to be infected with a chloroquine-resistant strain strengthened the evidence of a protective effect of chloroquine. Complications occurred in 14% of patients; pregnant women were at higher risk of complicated malaria; the case-fatality rate was low (0.3%). It is concluded that chloroquine prophylaxis still may have--depending on the degree of chloroquine-resistance--a protective effect on the clinical features and this modulating effect needs to be further investigated.

Falciparum malaria, imported into The Netherlands, 1979-1988. I. Epidemiological aspects.

From 1979-1988, 427 patients with falciparum malaria were prospectively investigated for chloroquine resistance. About 90% were infected in sub-Saharan Africa. Of the 361 non-immune patients 235 were evaluable; in 158 (67%) chloroquine resistance of Plasmodium falciparum could be confirmed. Chloroquine sensitivity was found in 77 (32%) patients. Sulfadoxine-pyrimethamine resistance was found in 33 patients. The history of use of chemoprophylaxis was recorded in 357 patients: 168 (49%) took adequate, 103 inadequate and 86 no chemoprophylaxis. In 65 of the 168 patients with a history of good compliance, prophylactic serum concentrations could be measured; in 56 (86%) patients the history was confirmed by the chloroquine level. All but one of them were infected with a resistant P. falciparum strain. Of the 66 semi-immune patients, 60 were infected in their homeland; in 5 (8%) chloroquine resistance was found. Only 1 of the 60 patients had used adequate chemoprophylaxis and proved to be infected with a resistant P. falciparum strain. During the study the spread of drug resistance from East Africa to other parts of Africa could be observed. Monitoring for drug-resistant falciparum malaria in travellers returning from malaria-endemic areas is a helpful tool in predicting the evolution of drug resistance in that area. In the non-endemic area such monitoring is essential for optimal advice on treatment of patients and of chemoprophylaxis in travellers.

[Strongyloides infections in former prisoners of war in South-East Asia in the second World War; additional information from serological diagnosis]. / Strongyloides-infecties bij voormalige krijgsgevangenen in Zuidoost-Azië in de Tweede Wereldoorlog; extra informatie door serologische diagnostiek.

OBJECTIVE: To analyse the efficacy of ELISA serology in patients with Strongyloides infection acquired during World War II and maintained through repeated autoinfection. DESIGN: Descriptive. SETTING: Laboratory of Parasitology, Faculty of Medicine, Leiden, the Netherlands. METHODS: Parasitological and clinical data on 193 ex-prisoners of war (South-east Asia) were presented previously (1990) by Verburg and De Geus. ELISA using L-3 S. ratti antigen was carried out with sera of these patients and the results were compared with those of repeated stool examinations using Baermann's method. RESULTS: All subjects harbouring larvae in repeated stool examinations (26) were positive in serology. In 21 out of 167 patients in whom no larvae could be demonstrated, specific antibodies were detected. Anamnestic information together with data on eosinophilia and IgE levels suggested that the majority of these subjects were actually infected. The serological prevalence of infection with Strongyloides stercoralis was 33% for those imprisoned in Burma and 4% for those who were prisoners of war in the former Netherlands East Indies. CONCLUSION: In the group of subjects studied, in whom Strongyloides infection was apparently maintained through a process of autoinfection for a period of over 40 years, serology appears a sensitive and specific diagnostic tool. Larvae could be detected in no more than 26 out of 47 serologically positive subjects.

Malaria chemosuppression during pregnancy. VI. Some epidemiological aspects of malaria in infants.

The possible influence of maternal malaria prophylaxis on infancy malaria was assessed in 241 infants. Mothers of 91 infants (PROG-cohort), 99 infants (CQ-cohort) and 51 infants (CQ+PROG-cohort) had received prophylaxis with daily proguanil, once weekly chloroquine, and the two drug combination respectively. Blood smears of infants were examined for parasitaemia once fortnightly. Parasitaemias were treated with either amodiaquine, Fansidar, or Fansidar-quinine combination. In all cohorts, the incidence of malaria parasitaemias within 3 months of age was high (overall mean = 63%). Chloroquine released from its tissue bound form in the CQ and CQ+PROG-cohorts did not have significant chemosuppressive effects on the parasitaemias. Acknowledging that the CQ-prophylaxis group simulated the hypothetical control group, the cohorts similarity in the pattern of parasitaemias suggested that effective maternal malaria chemoprophylaxis during pregnancy did not significantly influence infancy malaria. A sharp rise in incidence around 3 months was indicative of the waning effect of passive immunity. Sole dependence on sub-optimal active immunity led to another sharp rise in incidence from 9 months onwards. The high incidence of infancy malaria parasitaemias calls for increased vigilance in their early detection and effective treatment. Social-cultural factors within the communities may constrain effective disease management.

Comparison of three regimens for malaria prophylaxis in travellers to east, central, and southern Africa.

OBJECTIVES: Confirmation of breakthroughs in three different malaria chemoprophylactic regimens (chloroquine 300 mg weekly and proguanil 100 mg daily; chloroquine 300 mg weekly and proguanil 200 mg daily; proguanil 200 mg daily) and assessment of compliance. DESIGN: Prospective, randomised multicentre trial. SETTING: Five vaccination centres in the Netherlands. SUBJECTS: Dutch travellers to east, central, and southern Africa. MAIN OUTCOME MEASURES: Plasmodium falciparum seen on blood film; concentrations of drugs measured in blood spots. RESULTS: P falciparum infection was confirmed in 12 (21%) of 58 travellers with fever suspected to be due to malaria. No difference in prophylaxis failures between the regimens was found. Breakthroughs were difficult to confirm, as compliance could be determined in only 30% of the participants with fever and chloroquine in their regimen. One breakthrough was proved. The risk per 1000 people per month for travellers was 5.4 (95% confidence interval 2.4 to 12.6) for chloroquine 300 mg weekly and proguanil 100 mg daily, 2.8 (0.9 to 10.1) for chloroquine 300 mg weekly and proguanil 200 mg daily, and 6.0 (2.6 to 14.0) for proguanil 200 mg daily. CONCLUSION: Prophylaxis failures occurred in less than 1% of the participants, and only 21% of those with a fever were suffering from falciparum malaria. Compliance was moderate. The chloroquine-proguanil combination can still be recommended for visitors to east, central, and southern Africa.

Malaria chemosuppression in pregnancy. I. The effect of chemosuppressive drugs on maternal parasitaemia.

A randomized prophylactic drug trial was conducted in a malaria holoendemic area, in the Muheza District of Tanzania. Of 327 pregnant women, 124 received proguanil (PROG), 113 chloroquine (CQ), 90 the proguanil and chloroquine combination (CQ+PROG). Prophylaxis was supervised. Chemosuppressive efficacy was measured through the incidence of malaria breakthrough parasitaemias and clinical episodes. Groups were comparable by age, parity, residential area, and enrollment gestational age. Compliance and drug bio-availability was good. The median breakthrough time of the first parasitaemia episode for primigravidae (PG) and multigravidae (MG) was significantly shorter for the CQ group (PG = 56, MG = 78 days) than in the PROG (PG = 97, MG = 112 days) and the CQ+PROG (PG = 138, MG = 140 days) groups. 56% of the CQ group experienced 2 or more clinical episodes compared to 19% (PROG) and 10% (CQ+PROG). PROG and CQ+PROG did not differ significantly. Parasite densities and in vitro tests suggested that CQ selected for more and highly resistant strain(s). Proguanil is suitable for prophylaxis. However, proguanil resistance should be monitored as well as controlled drug distribution and usage. Malaria control strategies other than chemoprophylaxis should be investigated.

Malaria chemosuppression in pregnancy. III. Its effects on the maternal malaria immunity.

The malaria immune status of pregnant women participating in a malaria prophylaxis study was assessed using their sera reactivity to the R32tet32 antigen. Supervised prophylaxis started early in pregnancy till delivery. Women randomly received either chloroquine once weekly (CQ), or proguanil daily (PROG), or a combination of the two drugs (CQ + PROG). Blood was collected at enrollment, then after 8, 16, and 24 weeks of prophylaxis. Of the 312 women who received prophylaxis for more than 10 consecutive weeks before delivery, anti-sporozoite antibodies were assayed in 232 at enrollment, 258 after 8 weeks, and 254 after 16 weeks. Titres at enrollment were comparable by parity and the residential area. Antibodies in women of the PROG group who were parasitaemic before the assessments decreased with the increasing number of breakthrough and clinical episodes. The converse was true for antibodies in the CQ and CQ + PROG groups. Group differences in the parasite densities would explain this. Parity and placental malaria did not influence titres significantly. Overall, antibodies of the CQ + PROG group decrease significantly with time, possibly due to its long period of aparasitaemia. This suggested interference with the immune responsiveness of the women. PROG, which was equally efficacious, offers better prophylaxis.

Malaria chemosuppression in pregnancy. II. Its effect on maternal haemoglobin levels, placental malaria and birth weight.

The malaria prophylactic effects of chloroquine (CQ), proguanil (PROG), and chloroquine-proguanil combination (CQ+PROG) during pregnancy on maternal haemoglobin levels (Hb), placental malaria, and birth weight were assessed in Muheza, Tanzania. Within 2 months of prophylaxis, severe anaemia in primigravidae (PG) was reduced from 21% (22 cases) to 13% (13 cases). There was no positive effect in multigravidae (MG). Sustained increases in the mean Hb occurred in PG of the PROG and CQ+PROG groups. The mean Hb of PG of the CQ group decreased after an initial increase, possibly due to the selection of more and highly chloroquine-resistant strain(s). The mean birth weight of PG was highest in the CQ+PROG (2.89 kg) and least in the CQ group (2.71 kg). The CQ group had the highest low birth weight rate (LBW). The prevalence of placental malaria was highest in the CQ (28%) and lowest in the PROG group (12%). For all the prophylactic effects, PROG and CQ+PROG did not differ significantly. Thence, the deployment of CQ+PROG for prophylaxis would be unnecessary. Proguanil is a suitable alternative to chloroquine prophylaxis. Due to possible emergence of proguanil resistance, deployment of this drug should incorporate constant monitoring for resistance and the eventual prophylaxis efficacy. The search for other effective malaria control measures should continue.

Malaria chemosuppression during pregnancy. IV. Its effects on the newborn's passive malaria immunity.

The effect of malaria prophylaxis during pregnancy on the levels of cord blood anti-sporozoite antibodies was investigated in 203 newborns in Muheza, Tanzania. Mothers of 76 newborns had received prophylaxis with proguanil daily (PROG), 66 chloroquine once weekly (CQ), and 61 got a combination of the two drugs (CQ+PROG). Prophylaxis with PROG or CQ+PROG was more efficacious than with CQ. The mean antibody titres were comparable in all three groups, despite titres being significantly low in mothers of the CQ+PROG group. In 93% of 167 paired maternal-cord sera, maternal titres were higher than cord titres. The correlation between maternal and cord titres was low. Parity, placental malaria, and baby maturity showed little influence on titres. Titres of babies delivered by Caesarean section or whose placenta weighed between 0.75 and 1 kg were comparatively low. The first occurrence of a malaria parasitaemia in infants was independent of the levels of cord titres at birth. The results suggested that chemoprophylaxis as effective as PROG or CQ+PROG in holoendemic areas, insignificantly affects maternal-foetal transfer of anti-sporozoite antibodies, and that levels of these antibodies at birth do not modulate the first occurrence of infancy malaria parasitaemia. Interference with the maternal-foetal transfer of this antibody and possibly other component antibodies of passive immunity should not limit the selection of PROG or CQ+PROG for chemoprophylaxis.

Malaria chemosuppression in pregnancy. V. Placenta malarial changes among three different prophylaxis groups.

The effect of malaria chemoprophylaxis during pregnancy on placenta malarial changes (PMCs) was investigated in 170 tissue sections. Women of 63 sections received daily proguanil (PROG), 61 once weekly chloroquine (CQ) and 46 the two drug combination (CQ+PROG). All were residents of a malaria hyperendemic area in Muheza District, Tanzania. Supervised prophylaxis started early in pregnancy till delivery. Parasitaemias and clinical episodes were detected early and radically treated. Overall, PMCs were mostly infrequent and light viz: fibrinous deposits (98%), fibrinoid necrosis (60%), leucocytic infiltrations (59%), macrophage containing pigment (16%), and malaria parasites (8%). The type, prevalence, and severity of the PMCs in the three prophylaxis groups were comparable. This was despite the fact that PROG and CQ+PROG were prophylactically more efficacious than CQ and despite the expectation that the prevalence and severity of the PMCs would be high in the CQ group. Prompt diagnosis and effective treatment of parasitaemias in this group contributed to the low prevalence and less severity. It is concluded that effective malaria chemoprophylaxis or prompt diagnosis and effective treatment of malaria parasitaemias have significant impact on the prevalence of PMCs. Due to various operational constraints in most developing countries, chemoprophylaxis remains the only feasible broad option for malaria control in pregnancy.

PIP: The study area was Muheza District, north-eastern Tanzania, where some study participants delivering at Muheza District Hospital were matched with non-participants delivering at the same hospital (controls). Comparison of pathologies in the 3 prophylaxis groups was based on the results of 170 randomly selected placenta tissue sections (63 daily proguanil (PROG), 61 once weekly chloroquine (CQ), and 46 CQ+PROG) from women who received prophylaxis for more than 10 consecutive weeks before delivery. The histological features in decreasing order of frequency were: fibrinous deposits (98%), excessive fibrinoid with a possible damage to the villi (villus atrophy) (60%), leucocytic infiltrations (59%), macrophage containing pigment (16%), and lastly malaria-infected red blood cells (8%). Most placenta malarial changes (PCMs) were not associated with major destruction of placenta structures, and parasites did not adhere on the syncytiotrophoblast. Villi atrophy was found in only a few sections with fibrinous deposits. Overall, there were no significant differences in the frequencies of various components of placenta histology by parity and the maternal malaria prophylaxis regimen during pregnancy (p 0.05). In all groups, pathologies were mostly light. The frequency of classes in the 3 prophylaxis groups did not differ significantly (p 0.05). Overall, 133 (78%) of all placentae had no evidence of active or passed infection, while 24 (14%) had signs of past malaria infection and 13 (8%) had signs of active infection. The results of microscopic examination for malaria parasites in the placenta using the placental blood smear were compared with those obtained from the histological examination of the placenta tissue. Only 154 paired histology-blood smear examinations were possible. Examination of placental blood smears revealed twice as many placentae with malaria parasites as those detected by the histological examination of the placenta tissue (p 0.01). The 2 examinations gave the same results in 115 pairs (7 positive and 118 negatives) and differed in 29 pairs (23 smear positive but tissue negative, while 6 were tissue positive but smear negative).

Malaria in infants whose mothers received chemoprophylaxis: response to amodiaquine therapy.

In October 1988, a project was implemented for assessing the malaria chemoprophylactic efficacy of weekly chloroquine (CQ) and daily proguanil (PROG) during pregnancy in Muheza-Tanzania. Resultant CQ and PROG-cohorts of infants were followed up for prompt diagnosis and treatment of malaria. Infections were primarily treated with 25 mg base amodiaquine/kg over 3 days. By September 1990, 49 and 60 infants from PROG and CQ cohorts respectively had completed one year follow up. Thirty-five (71%) infants of PROG and 44 (73%) for CQ-cohort were infected with malaria before 3 months of age. The one year mean infection episode rates were 7 (PROG-cohort) and 6.6 (CQ-cohort). Amodiaquine cleared 209 (80%) of PROG's total infections and 224 (81%) for CQ-cohort, and significantly reduced the infection load among clearance failures. Clearance failures had high pre-treatment parasite densities whilst post-treatment densities were higher in the CQ-cohort than PROG-cohort. Low malaria immunity and chloroquine's long residence time could explain these differences. We conclude that early infancy malaria is common and should always be suspected, looked for and adequately treated. Amodiaquine is better than chloroquine for malaria primary therapy during infancy and early childhood.