Effect of haematinic supplementation and malaria prevention on maternal anaemia and malaria in western Kenya

OBJECTIVE: To evaluate the effect of routine antenatal haematinic supplementation programmes and intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) in Kenya. METHODS: Anaemia [haemoglobin (Hb) <11 g/dl), severe anaemia (Hb <8 g/dl) and placental malaria were compared among women with known HIV status who delivered at a provincial hospital after study enrolment in the third trimester during three consecutive periods: period 1, no routine intervention (reference); period 2, routine haematinic supplementation (60 mg elementary iron three times/day, folic acid 5 mg once daily) and period 3, haematinics and IPT with SP. RESULTS: Among 3108 participants, prevalence of placental malaria, anaemia and severe anaemia postpartum was 16.7%, 53.6% and 12.7%, respectively. Compared with period 1, women in period 2 were less anaemic [adjusted odds ratio (AOR), 95% confidence interval anaemia: 0.56, 0.47-0.67; severe anaemia 0.37, 0.28-0.49] and shared a similar prevalence of placental malaria (AOR 1.07, 0.86-1.32). Women in period 3 were also less anaemic (AOR anaemia: 0.43, 0.35-0.53 and severe anaemia: 0.43, 0.31-0.59), and had less placental malaria (AOR 0.56, 0.42-0.73). The effect of intervention did not differ significantly by HIV status. CONCLUSION: The haematinic supplementation programme was associated with significant reductions in anaemia in HIV-seropositive and HIV-seronegative women. The subsequent introduction of IPT was associated with halving of malaria, but no additional haematological benefit over haematinics.     

Severe anaemia in children living in a malaria endemic area of Kenya

Severe anaemia is an important cause of morbidity and mortality in African children, but the causes, particularly falciparum malaria, are difficult to determine. We assessed the contribution of falciparum malaria to anaemia in Kenyan children by clinical examination and measurement of parasitaemia and haemoglobin (Hb) concentration in 559 children in the community and in 2412 children admitted to Kilifi district hospital during a 2‐year period. We also attempted to characterize severe malarial anaemia by examining the causes and pathophysiology of anaemia in 101 children admitted with Hb concentration 50 g/l during a 1‐year period. Plasmodium falciparum infection was associated with reduced Hb concentration in children in the community and in those admitted to hospital irrespective of diagnosis. Falciparum malaria was the primary cause in 46 cases (46%) of severe anaemia admitted to hospital. There was no difference in the frequency of haemolysis or dyserythropoiesis in the children with malarial anaemia and those with anaemia from other causes, such as iron deficiency or sickle cell disease. The mortality rate in the children with severe malarial anaemia was 8.6% compared with 3.6% in children with severe anaemia due to other causes. Falciparum malaria does not present with a characteristic clinical or haematological picture, but is a major cause of the morbidity and mortality in children with severe anaemia who live on the Kenyan coast, a malaria endemic area.     

Malaria and anaemia among pregnant women at first antenatal clinic visit in Kisumu, western Kenya

Objective To determine the prevalence of malaria and anaemia among urban and peri‐urban women attending their first antenatal clinic (ANC) in an area of perennial malaria transmission. Methods Between November 2003 and May 2004 we screened first ANC attenders for malaria and anaemia in a large urban hospital in Kisumu (western Kenya) and interviewed them to obtain demographic and medical information. Results Among the 685 study participants, prevalence of malaria parasitaemia was 18.0%, prevalence of any anaemia (haemoglobin < 11 g/dl) was 69.1% and prevalence of moderate anaemia was (haemoglobin < 8 g/dl) 11.8%. Sixteen women were hospitalized during pregnancy, eight because of malaria. In multivariate analysis, young age, living in a house with mud walls, a visit to rural area, peri‐urban residence, second trimester of pregnancy and Luo ethnicity were significant risk factors for malaria parasitaemia. Malaria was an important risk factor for any and moderate anaemia; use of an insecticide‐treated net (ITN) was a protective factor for any anaemia. Married women with a higher level of education, better‐quality housing and full‐time employment were more likely to use an ITN. Conclusion Malaria and anaemia are established problems by the time of the first ANC visit. Mechanisms to deliver ITNs to women of child‐bearing age before they become pregnant need to be explored. Early ANC visits are warranted in order for women to benefit from policies aimed at reducing the burden of malaria and anaemia.     

Geophagy, iron status and anaemia among primary school children in Western Kenya

As part of a cross-sectional study among 156 primary school children (median age 13 years, range 10–18) in Western Kenya, geophagy was assessed through interviews. 114 (73.1%) of these children reported eating soil daily. Haemoglobin levels were determined in all 156 children and serum ferritin concentrations in 135. The mean haemoglobin (Hb) concentration was 12.7 g/dl, and median ferritin concentration 27.2 μg/l. Both the proportion of anaemic (Hb < 11.0 g/dl) and of iron-depleted (ferritin < 12 μg/l) children was significantly higher among the geophageous children than among the nongeophageous (9.6%vs. 0% anaemia; P= 0.037; 18.4%vs. 5.4% iron depletion; P= 0.046). Serum ferritin and haemoglobin concentrations were not correlated (r= 0. 13 5; P= 0. 100). Multiple regression analysis showed that geophagy, hookworm eggs per gram faeces and malaria parasite counts per μl blood were independent predictors of serum ferritin, when controlling for other helminth infections, age and sex, and socio-economic and educational background of the children's families and family size (y = 36.038–11.247(geophagy) – 0.010(hookworm epg) + 0.001(malaria parasite counts); R^{2 = 0.17). Multiple regression analysis with haemoglobin as dependent variable and the same independent variables did not reveal any significant predictors. Analysis of the soil eaten by the children revealed a mean HCl-extractable iron content of 168.9 mg/kg (SD 44.9). Based on the data on the amounts eaten daily and this mean iron content, soil could provide on average 4.7 mg iron to a geophageous child (interquartile range 2.1–7.1 mg), which is equivalent to 32% of the Recommended Nutrient Intake (RNI) for girls (interquartile range 14–48%) or 42% of the RNI for boys (interquartile range 19–63%). Iron depletion and anaemia are associated with geophagy, but only serum ferritin concentrations were shown to be dependent upon geophagy in the regression model. From the cross-sectional data no inference about causality can be made. To clarify the possible causal relationships involved, longitudinal studies and iron-supplementation intervention studies are needed.}     

Recognition of pallor associated with severe anaemia by primary caregivers in western Kenya

OBJECTIVES: To explore which pallor signs and symptoms of severe anaemia could be recognized by primary caregivers following minimal instructions. METHODS: Data from three community-based cross-sectional surveys were used. Test characteristics to predict haemoglobin (Hb) concentrations < 5 and < 7 g/dl were compared for different combinations of pallor signs (eyelid, tongue, palmar and nailbed) and symptoms. RESULTS: Pallor signs and haemoglobin levels were available for 3782 children under 5 years of age from 2609 households. Comparisons of the sensitivity and specificity at a range of haemoglobin cut-offs showed that Hb < 5 g/dl was associated with the greatest combined sensitivity and specificity for pallor at any anatomical site (sensitivity = 75.6%, specificity = 63.0%, Youden index = 38.6). Higher or lower haemoglobin cut-offs resulted in more children being misclassified. Similar results were obtained for all individual pallor sites. Combining a history of soil eating with pallor at any site improved the sensitivity (87.8%) to detect Hb < 5 g/dl with a smaller reduction in specificity (53.3%; Youden index 41.1). Other combinations including respiratory signs or poor feeding resulted in lower accuracy. CONCLUSION: Primary caregivers can recognize severe anaemia (Hb < 5 g/dl) in their children, but only with moderate accuracy. Soil eating should be considered as an additional indicator of severe anaemia. The effect of training caretakers to improve recognition of severe anaemia and care-seeking behaviour at the household level should be assessed in prospective community-based studies.     

Higher resistance to Plasmodium falciparum infection in patients with homozygous sickle cell disease in western Kenya

Sickle haemoglobin (HbS) is considered to be protective against malaria. Malaria is fatal in homozygous sickle cell (HbSS) disease. In a cross‐sectional survey by alkaline Hb‐electrophoresis of 766 residents of Western Kenya near Lake Victoria, 20 were found to have HbSS disease, 120 sickle cell trait (HbAS) and 626 the normal genotype (HbAA). Blood slides for malarial parasites (MPs) were performed in 728 cases, i.e. 592 HbAAs, 116 HbASs and all 20 HbSSs. Malaria parasites were found in 261 (35.8%) HbAAs, 42 (5.8%) HbASs and 4 (0.5%) HbSSs. Malaria prevalences per genotypic group were 44.1% (261 out of 592) in HbAAs, 36.2% (42 out of 116) in HbASs, and 20% (4 out of 20) in HbSSs. The relative risk of malarial infection was 0.33 in the HbSSs compared to both HbAAs and HbASs. It seems that the protection conferred by HbS against malaria is more marked in HbSS disease than in HbAS and is HbS‐content related, and that the balanced polymorphism in the HbS–malaria relationship is maintained by higher mortality risk of HbAAs due to malaria and high mortality risk of HbSSs caused by complications of HbSS.     

Severe anaemia in Zambian children with Plasmodium falciparum malaria

BACKGROUND: Severe anaemia and cerebral malaria are highly prevalent complications of Plasmodium falciparum malaria among African children. The mechanisms of severe malarial anaemia, and the relative importance of this condition in comparison to cerebral malaria, are not known for many regions of Africa. METHODS We reviewed the records of 6200 children up to 6 years of age admitted to one rural Zambian hospital between 1994 and 1996. Severe malarial anaemia was defined as an haemoglobin concentration < 5.0 g/dl in a patient with asexual forms of P. falciparum in the peripheral blood. Cerebral malaria was defined as impaired consciousness (Blantyre coma score < 5) not attributable to any other cause in a patient with a positive malaria smear. RESULTS Severe malarial anaemia was found in 590 children (9.5% of paediatric admissions) and strictly defined cerebral malaria occurred in 286 children (4.6% of paediatric admissions); 98 of these patients had the combination of both complications. Severe malarial anaemia correlated strongly with the degree of parasitaemia, with malnutrition as indicated by low weight for age, with absence of fever and with presentation late in the malaria season. In comparison, patients with cerebral malaria were more often febrile and presented earlier in the malaria season. The case fatality rate of severe malarial anaemia (0.088) was about half that of cerebral malaria (0.189), but because severe malarial anaemia was more common, these two forms of complicated malaria were implicated in similar numbers of in-hospital paediatric deaths. CONCLUSION Severe anaemia is a more common complication of P. falciparum malaria in hospitalized Zambian children than cerebral malaria and is associated with a similar number of deaths. Malnutrition and changes in immune response patterns due to prolonged exposure to P. falciparum may contribute to the development of this complication.     

In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya

Objectives  To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya.
Methods  Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6–59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria.
Results  The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrolment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences.
Conclusion  Although artemether-lumefantrine (Coartem^®) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an effective alternative to Coartem^® in western Kenya. Continued amodiaquine monotherapy in the private sector may jeopardise the future use of amodiaquine-artesunate as an alternative artemisinin-based combination therapy.     

Plasmodium falciparum multiplicity correlates with anaemia in symptomatic malaria

In 366 Ghanaian children with symptomatic Plasmodium falciparum malaria, low haemoglobin levels and severe anaemia were associated with a high multiplicity of infection (MOI) and with distinct merozoite surface protein alleles. High MOI not only reflects premunition but may also contribute to anaemia in symptomatic malaria.     

Effectiveness of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in western Kenya: a hospital-based study

OBJECTIVE: To monitor the effectiveness of intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) for the control of malaria in pregnancy at delivery in the Provincial Hospital in Kisumu, Kenya, and to assess the effect of IPT in participants in a cohort study. METHODS: Between June 1999 and June 2000, information on IPT and birth outcome was collected in 2302 consecutive deliveries. A group of 889 women, who were enrolled in a cohort to assess the interaction between malaria and HIV, were analysed separately because of the enrollment criteria and different access to health care. RESULTS: The prevalence of placental malaria was 13.8% and of low birthweight (LBW) was 12.2%. In multivariable analysis, IPT (> or =1 dose of SP) was associated with a reduction in placental malaria and LBW [adjusted odds ratio (OR) 0.56, 95% confidence interval (CI) 0.39-0.83 and OR 0.65, 95% CI 0.45-0.95, respectively]. An adjusted mean increase in birthweight of 61 g was seen (95% CI 22-101 g) for each increment in number of SP doses (> or =2 doses grouped together). IPT was associated with a reduction in placental malaria in HIV-seronegative women (OR 0.49, 95% CI 0.28-0.86) but this was not significant among HIV-seropositive women (OR 0.45, 95% CI 0.20-1.05). A significant effect on birthweight could not be detected among participants in the HIV-cohort. CONCLUSIONS: This evaluation confirms that IPT with SP is effective in reducing placental malaria and LBW. It will be important to increase coverage of IPT and to extend IPT to antenatal clinics in peri-urban and rural areas.     

Low larval vector survival explains unstable malaria in the western Kenya highlands

Several highland areas in eastern Africa have recently suffered from serious malaria epidemics. Some models predict that, in the short term, these areas will experience more epidemics as a result of global warming. However, the various processes underlying these changes are poorly understood. We therefore investigated malaria prevalence, malaria vector densities and malaria vector survival in a highland area in western Kenya, ranging from approximately 1550–1650 m altitude. Although only five adult malaria vectors were collected during 180 light traps and 180 resting collections over a 23‐month study period, malaria was prevalent among school children (average parasite prevalence: 10%). During an extensive survey of potential larval habitats, we identified only seven habitats containing Anopheles gambiae Giles s.l. larvae. Their limited number and low larval densities suggested that their contribution to the adult vector population was small. Experiments on adult and larval survival showed that at this altitude, adult mosquitoes survived inside local houses, but that larval development was severely retarded: only 2 of 500 A. gambiae s.l. larvae developed to the pupal stage, whereas all other larvae died prior to pupation. At present, high vector densities are unlikely because of unfavourable abiotic conditions in the area. However, temporary favourable conditions, such as during El Niño years, may increase larval vector survival and may lead to malaria epidemics.     

Spatial clustering of malaria and associated risk factors during an epidemic in a highland area of western Kenya

The epidemiology of malaria over small areas remains poorly understood, and this is particularly true for malaria during epidemics in highland areas of Africa, where transmission intensity is low and characterized by acute within and between year variations. We report an analysis of the spatial distribution of clinical malaria during an epidemic and investigate putative risk factors. Active case surveillance was undertaken in three schools in Nandi District, Western Kenya for 10 weeks during a malaria outbreak in May-July 2002. Household surveys of cases and age-matched controls were conducted to collect information on household construction, exposure factors and socio-economic status. Household geographical location and altitude were determined using a hand-held geographical positioning system and landcover types were determined using high spatial resolution satellite sensor data. Among 129 cases identified during the surveillance, which were matched to 155 controls, we identified significant spatial clusters of malaria cases as determined using the spatial scan statistic. Conditional multiple logistic regression analysis showed that the risk of malaria was higher in children who were underweight, who lived at lower altitudes, and who lived in households where drugs were not kept at home.     

Prolonged macrophage activation and persistent anaemia in children with complicated malaria

objective   To determine if prolonged immune activation may be associated with the persistence of anaemia after treatment for severe malaria, we measured serum concentrations of neopterin and interleukin-4 during one week of antimalarial therapy and determined haemoglobin levels one month later. Neopterin is a clinically valuable marker for monitoring activation of macrophages by gamma-interferon and thus reflects the TH-1 immune response. Interleukin-4 is a major cytokine that tends to be inhibited by TH-1 activity. method   The study population consisted of 26 Zambian children <6 years of age who presented with cerebral malaria to a rural hospital in 1994 and who were treated with quinine for seven days. Six children (23%) were anaemic (haemoglobin < 11 g/dl) one month after completing antimalarial therapy. results   On admission, concentrations of neopterin were markedly elevated in all patients. During the seven days of anti-malarial therapy, neopterin levels remained elevated in the 6 children who proved to have persistent anaemia one month after finishing treatment but declined significantly ( P = 0.008) in the 20 children who corrected their haemoglobin levels by that time. Conversely, interleukin-4 levels declined in the children with persistent anaemia ( P = 0.043) but not in the other children. conclusion   Persistence of the TH-1 mediated immune response and associated activation of macrophages may be involved in the pathogenesis of lingering anaemia after treatment of malaria.     

Use of intermittent preventive treatment for malaria in pregnancy in a rural area of western Kenya with high coverage of insecticide-treated bed nets

Kenya established intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) for malaria in pregnancy as national policy in 1998. We assessed the coverage of IPT among women who had recently delivered in a rural area of western Kenya with perennial malaria transmission and high coverage with insecticide treated nets (ITNs) through a cross-sectional, community-based survey in December 2002. Antenatal clinic (ANC) attendance was high (89.9% of the 635 participating women); 77.5% of attendees visited an ANC before the third trimester and 91.9% made more than one visit. Delivery of SP by the ANC was reported by 19.1% of all women but only 6.8% reported receiving more than one dose. Given the high rate of use of ANC services, if SP were given at each visit after the first trimester, the potential coverage of IPT (two doses of SP) would be 80.3% in this study population. ITNs were used by 82.4% of women during pregnancy, and almost all mothers (98.5%) who slept under an ITN shared the nets with their newborns after delivery. Women who thought malaria in pregnancy caused foetal problems were more likely to have used an ITN (adjusted odds ratio [AOR] 1.6, 95% confidence interval [CI] 1.0-2.4), and to have visited ANC more than once (AOR 2.4, 95% CI 1.2-4.7) compared to women who thought malaria in pregnancy was either not a problem or caused problems for the mother only. These findings illustrate the need for improved IPT coverage in this rural area. Identification and removal of the barriers to provision of IPT during ANC visits can help to increase coverage. In this area of Kenya, health messages stressing that foetal complications of malaria in pregnancy may occur in the absence of maternal illness may improve the demand for IPT.     

Relationship between haemoglobin and haematocrit in the definition of anaemia

Introduction Anaemia is the most frequent haematological disorder in childhood. The notion that defines naemia does not change throughout life, although parameters used for its evaluation show significant variations during childhood. Haematocrit (Hct) (%) is usually defined as three times the value of haemoglobin (Hgb) (g/dl), while the clinical definition of anaemia is related to either an abnormal Hct or Hgb value. Objective To evaluate the agreement between Hgb and Hct values in the definition of anaemia, the relationship between these two parameters and their age‐dependence. Methods The Hct and Hgb paired values from children aged 2–18 months from Ifakara (Tanzania) and children aged 1–4 years from Manhiça (Mozambique) were analysed. Haematological determinations of the Manhiça samples were done using a KX‐21N cell counter (Kobe, Japan) and Ifakara samples were analysed in a semiautomatic cell counter (Sysmex F800 microcell counter, TOA Medical Electronics, Kobe, Japan). The κ‐statistic was used to calculate the agreement between anaemia definitions in each group. Crude and multivariate relationship between Hct and Hgb levels were analysed by linear regression model estimation. The age‐dependence of the crude ratio (Hct/Hgb) was analysed using linear regression models and fractional polynomials. Results The prevalences of mild and moderate anaemia as defined by Hgb levels in the Manhiça group were 61% and 6%, respectively, and 41% and 2% by Hct. In the Ifakara group these were 74% and 10%, respectively, by Hgb and 42% and 3% by Hct, respectively. Agreement between mild and moderate anaemia definitions made up from Hgb or from Hct levels were from fair to moderate. Hct levels decreased with age for high Hgb levels, whereas they increased for low Hgb levels. The classification of cases is improved when higher age‐related cut‐off values for Hct are used. The crude relationship between Hct and Hgb levels was significantly different from 3, and this was modified by age. The evaluation of the age‐dependence ratio (Hct/Hgb) showed a non‐linear relationship with an asymptotic trend to 3. Conclusions Measurement of haematocrit count is easy and can be performed in most rural health care centres. However, the corresponding Hgb levels cannot be derived with an acceptable accuracy using the value 3 as a conversion factor. Furthermore, the commonly assumed ‘equivalent’ cut‐off points for anaemia definitions need to be re‐evaluated.     

Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia

Plasmodium falciparum infection can lead to deadly complications such as severe malaria-associated anaemia (SMA) and cerebral malaria (CM). Children with severe malaria have elevated levels of circulating immune complexes (ICs). To further investigate the quantitative differences in antibody class/subclass components of ICs in SMA and CM , we enrolled 75 children with SMA and 32 children with CM from hospitals in western Kenya and matched them to 74 and 52 control children, respectively, with uncomplicated symptomatic malaria. Total IgG IC levels were always elevated in children with malaria upon enrolment, but children with CM had the highest levels of any group. Conditional logistic regression showed a borderline association between IgG4-containing IC levels and increased risk of SMA (OR = 3·11, 95% CI 1·01–9·56, P  = 0·05). Total IgG ICs (OR = 2·84, 95% CI 1·08–7·46, P  = 0·03) and IgE-containing ICs (OR = 6·82, OR 1·88–24·73, P  ≤ 0·01) were associated with increased risk of CM. These results point to differences in the contribution of the different antibody class and subclass components of ICs to the pathogenesis of SMA and CM and give insight into potential mechanisms of disease.     

Implementation of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in Kisumu, western Kenya

OBJECTIVE: In 1998, the Kenyan Ministry of Health introduced intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), one treatment dose in the second trimester (16-27 weeks) and one treatment dose between 28 and 34 weeks of gestational age, for the control of malaria in pregnancy. We evaluated the coverage and determinants of receipt of IPT after its introduction in the Provincial Hospital in Kisumu, western Kenya. METHODS: Information on the use of IPT in pregnancy was collected from women who attended the antenatal clinic (ANC) and delivered in the same hospital. In exit interviews, we assessed patterns of IPT use in the ANC. RESULTS: Of 1498 women who delivered between June 1999 and June 2000, 23.7%, 43.4% and 32.9% received > or =2, 1 or no dose of SP, respectively. Late first ANC attendance was the most important factor contributing to incomplete IPT; 45% of the women started attending ANC in the third trimester. More women received at least one tetanus toxoid immunization than at least one dose of IPT (94%vs. 67%, P < 0.05). In exit interviews, 74% correctly associated IPT with treatment of malaria; however, knowledge on the need for the second dose was poor. Three per cent of the administrations were given despite contraindications. The agreement between gestational age by date of last menstrual period and by palpation was low (kappa = 0.1). CONCLUSIONS: Education of pregnant women and ANC staff to increase earlier attendance for ANC has the potential to substantially increase the proportion of women receiving two doses of IPT with SP.     

Spatial distribution of Burkitt's lymphoma in Kenya and association with malaria risk

Endemic Burkitt's lymphoma (BL) is the most common paediatric malignancy in equatorial Africa and was originally shown to occur at high-incidence rates in regions where malaria transmission is holoendemic. New ecological models of malaria that are based on both parasite prevalence and disease have been described. In this study, we examined district level data collected from paediatric BL cases in Kenya from 1988 through 1997 and assessed whether the distribution of district level incidence rates could be explained by new ecologic estimates of malaria risk. Chi-square tests and log-linear regression models were used to evaluate these associations. An association with tribe of origin as a factor also was examined. The 10-year average annual incidence rate (IR) for Kenya was 0.61 per 100,000 children. Incidence rates varied by malaria transmission intensity as follows: low malaria risk (BL IR = 0.39), arid/seasonal (0.25), highland (0.66), endemic coast (0.68), and endemic lake (1.23) (chi(2) = 11.32, P = 0.002). In a log-linear model, BL rates were 3.5 times greater in regions with chronic and intense malaria transmission intensity than in regions with no or sporadic malaria transmission (odds ratio = 3.47, 95% confidence interval = 1.30-9.30), regardless of tribe. Although crude tribe-specific incidence rates ranged between 0.0 and 3.26, tribe was not associated with BL after controlling for malaria. These findings support the aetiologic role of intense malaria transmission intensity in BL.     

Dyserythropoiesis and severe anaemia associated with malaria correlate with deficient interleukin-12 production

Complex cytokine interactions occur during blood-stage malaria which offer a unique opportunity to study their influence on the pathogenesis of malarial anaemia. Plasmodium chabaudi AS susceptible A/J mice experience severe and fatal anaemia whereas resistant C57BL/6 (B6) mice survive following moderate anaemia. In this study we analysed the role of IL-12 in erythropoiesis and tested whether the levels of IL-12 produced in these mice correlated with the extent of anaemia. In vitro , IL-12 significantly enhanced the numbers of erythroid burst (BFU-E) and colony forming units (CFU-E) in bone marrow and spleen cells from normal and day 7 infected A/J and B6 mice. Despite the presence of IL-12 in vitro , the level of splenic erythropoiesis in infected A/J mice was significantly lower than in B6 mice. Moreover, sera from infected B6 mice, but not A/J mice, significantly up-regulated erythropoiesis in vitro and this enhancement correlated with several fold higher levels of IL-12 in the sera of B6 compared to A/J mice. Furthermore, the erythropoietic potentiating effect of sera from infected B6 mice was abrogated following depletion of IL-12. Taken together, these findings suggest that defective IL-12 production in A/J mice during the early course of infection may result in fatal anaemia.     

Field efficacy of thermally expelled or live potted repellent plants against African malaria vectors in western Kenya

OBJECTIVE: To estimate the effectiveness of live potted plants and thermal expulsion of plant materials in repelling African malaria vectors in traditional houses in western Kenya. METHODS: Ocimum americanum, Lantana camara and Lippia ukambensis were tested in live, intact potted form whereas leaves of Corymbia citriodora, leaves and seeds of O. kilimandscharicum and O. suave were tested by thermal expulsion from modified traditional stoves. A latin square design was applied for randomly assigning the treatment and control plants to experimental houses over different nights. RESULTS: All plant species showed significant repellency against Anopheles gambiae sensu lato Giles (Diptera: Culicidae) (81.5%An. arabiensis Patton and 18.5%An. gambiae sensu stricto Giles), the main vectors of malaria in Africa, with the highest repellency by C. citriodora (48.71%, P < 0.0001) followed by an equal level of repellency of O. kilimandscharicum and O. suave (44.54%, P = 0.001) during application of plant material by thermal expulsion. All three plant species also showed a residual effect against An. gambiae s.l. with 36-44% repellency post-application period (22.30-06.30 hours) after a period of thermal expulsion. Similarly, intact potted plants of O. americanum and L. camara repelled An. gambiae s.l. significantly (37.91%, P = 0.004; and 27.22%, P = 0.05, respectively). Thermal expulsion of leaves and seeds of O. kilimandscharicum significantly repelled An. funestus Giles, although none of the potted plants repelled this species. CONCLUSION: Both methods of application may offer cost-effective alternatives as additional means of household protection, and a useful complement to bed nets, particularly for the early part of the evening before bedtime.