Allomonal effect of breath contributes to differential attractiveness of humans to the African malaria vector Anopheles gambiae

BACKGROUND: Removal of exhaled air from total body emanations or artificially standardising carbon dioxide (CO(2)) outputs has previously been shown to eliminate differential attractiveness of humans to certain blackfly (Simuliidae) and mosquito (Culicidae) species. Whether or not breath contributes to between-person differences in relative attractiveness to the highly anthropophilic malaria vector Anopheles gambiae sensu stricto remains unknown and was the focus of the present study. METHODS: The contribution to and possible interaction of breath (BR) and body odours (BO) in the attraction of An. gambiae s.s. to humans was investigated by conducting dual choice tests using a recently developed olfactometer. Either one or two human subjects were used as bait. The single person experiments compared the attractiveness of a person's BR versus that person's BO or a control (empty tent with no odour). His BO and total emanations (TE = BR+BO) were also compared with a control. The two-person experiments compared the relative attractiveness of their TE, BO or BR, and the TE of each person against the BO of the other. RESULTS: Experiments with one human subject (P(1)) as bait found that his BO and TE collected more mosquitoes than the control (P = 0.005 and P < 0.001, respectively), as did his BO and the control versus his BR (P < 0.001 and P = 0.034, respectively). The TE of P(1 )attracted more mosquitoes than that of another person designated P(8 )(P < 0.021), whereas the BR of P(8 )attracted more mosquitoes than the BR of P(1 )(P = 0.001). The attractiveness of the BO of P(1 )versus the BO of P(8 )did not differ (P = 0.346). The BO from either individual was consistently more attractive than the TE from the other (P < 0.001). CONCLUSIONS: We demonstrated for the first time that human breath, although known to contain semiochemicals that elicit behavioural and/or electrophysiological responses (CO(2), ammonia, fatty acids) in An. gambiae also contains one or more constituents with allomonal (~repellent) properties, which inhibit attraction and may serve as an important contributor to between-person differences in the relative attractiveness of humans to this important malaria vector

In utero exposure to malaria is associated with metabolic traits in adolescence: The Agogo 2000 birth cohort study.

OBJECTIVES: Malaria in pregnancy (MiP) contributes to fetal undernutrition and adverse birth outcomes, and may constitute a developmental origin of metabolic diseases in the offspring. In a Ghanaian birth cohort, we examined the relationships between MiP-exposure and metabolic traits in adolescence. METHODS: MiP at delivery was assessed in 155 mother-child pairs. Among the now teenaged children (mean age, 14.8 years; 53% male), we measured fasting plasma glucose (FPG), body mass index (BMI), and systolic and diastolic blood pressure (BP). Associations of MiP with the adolescents' FPG, BMI, and BP were examined by linear regression. RESULTS: At delivery, 45% were MiP-exposed, which increased FPG in adolescence, adjusted for mother's age at delivery, parity and familial socio-economic status (infected vs. uninfected: mean ΔFPG = 0.20 mmol/L; 95% confidence interval (CI): 0.01, 0.39; p = 0.049). As a trend,this was discernible for BP, particularly for microscopic infections (mean Δsystolic BP = 5.43 mmHg; 95% CI: 0.00, 10.88; p = 0.050; mean Δdiastolic BP = 3.67 mmHg; 95% CI: -0.81, 8.14; p = 0.107). These associations were largely independent of birth weight, gestational age and teenage BMI. Adolescent BMI was not related to MiP. CONCLUSIONS: In rural Ghana, exposure to malaria during fetal development contributes to metabolic conditions in young adulthood

Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy

<p>Abstract</p> <p>Background</p> <p>The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer <it>TIRAP </it>has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.</p> <p>Methods</p> <p>We assessed the <it>TIRAP </it>S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh.</p> <p>Results</p> <p>In Ghana, the <it>TIRAP </it>S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous <it>TIRAP </it>180L tend to increase the risk of sepsis in the German study (<it>P </it>= 0.04).</p> <p>Conclusion</p> <p>A broad protective effect of <it>TIRAP </it>S180L against infectious diseases <it>per se </it>is not discernible.</p

α-Thalassemia Impairs the Cytoadherence of Plasmodium falciparum-Infected Erythrocytes

α-Thalassemia results from decreased production of α-globin chains that make up part of hemoglobin tetramers (Hb; α(2)β(2)) and affects up to 50% of individuals in some regions of sub-Saharan Africa. Heterozygous (-α/αα) and homozygous (-α/-α) genotypes are associated with reduced risk of severe Plasmodium falciparum malaria, but the mechanism of this protection remains obscure. We hypothesized that α-thalassemia impairs the adherence of parasitized red blood cells (RBCs) to microvascular endothelial cells (MVECs) and monocytes--two interactions that are centrally involved in the pathogenesis of severe disease.We obtained P. falciparum isolates directly from Malian children with malaria and used them to infect αα/αα (normal), -α/αα and -α/-α RBCs. We also used laboratory-adapted P. falciparum clones to infect -/-α RBCs obtained from patients with HbH disease. Following a single cycle of parasite invasion and maturation to the trophozoite stage, we tested the ability of parasitized RBCs to bind MVECs and monocytes. Compared to parasitized αα/αα RBCs, we found that parasitized -α/αα, -α/-α and -/-α RBCs showed, respectively, 22%, 43% and 63% reductions in binding to MVECs and 13%, 33% and 63% reductions in binding to monocytes. α-Thalassemia was associated with abnormal display of P. falciparum erythrocyte membrane protein 1 (PfEMP1), the parasite's main cytoadherence ligand and virulence factor, on the surface of parasitized RBCs.Parasitized α-thalassemic RBCs show PfEMP1 display abnormalities that are reminiscent of those on the surface of parasitized sickle HbS and HbC RBCs. Our data suggest a model of malaria protection in which α-thalassemia ameliorates the pro-inflammatory effects of cytoadherence. Our findings also raise the possibility that other unstable hemoglobins such as HbE and unpaired α-globin chains (in the case of β-thalassemia) protect against life-threatening malaria by a similar mechanism

Reliability of Rapid Diagnostic Tests in Diagnosing Pregnancy-Associated Malaria in North-Eastern Tanzania.

Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen™) or HRP-2 only (Paracheck Pf® and ParaHIT®f), microscopy and nested Plasmodium species diagnostic PCR. From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 -1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 - 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool

Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women

<p>Abstract</p> <p>Background</p> <p>In sub-Saharan Africa, <it>Plasmodium falciparum </it>malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance of the different types of malaria diagnosis as well as risk factors associated with malaria infection at delivery were investigated.</p> <p>Method</p> <p>In a cross-sectional survey, 306 women reporting for delivery in the Mutenegene maternity clinic, Fako division, South West province, Cameroon were screened for <it>P. falciparum </it>in peripheral blood, placental blood and placental tissue sections by microscopy. Information relating to the use of intermittent preventive treatment in pregnancy with sulphadoxine/pyrimethamine, history of fever attack, infant birth weights and maternal anaemia were recorded.</p> <p>Results</p> <p>Among these women, <it>P. falciparum </it>infection was detected in 5.6%, 25.5% and 60.5% of the cases in peripheral blood, placental blood and placental histological sections respectively. Placental histology was more sensitive (97.4%) than placental blood film (41.5%) and peripheral blood (8.0%) microscopy. In multivariate analysis, age (≤ 20 years old) (OR = 4.61, 95% CI = 1.47 – 14.70), history of fever attack (OR = 2.98, 95% CI = 1.58 – 5.73) were significant risk factors associated with microscopically detected parasitaemia. The use of ≥ 2 SP doses (OR = 0.18, 95% CI = 0.06 – 0.52) was associated with a significant reduction in the prevalence of microscopic parasitaemia at delivery. Age (>20 years) (OR = 0.34, 95% CI = 0.15 – 0.75) was the only significant risk factor associated with parasitaemia diagnosed by histology only in univariate analysis. Microscopic parasitaemia (OR = 2.74, 95% CI = 1.33–5.62) was a significant risk factor for maternal anaemia at delivery, but neither infection detected by histology only, nor past infection were associated with increased risk of anaemia.</p> <p>Conclusion</p> <p>Placenta histological examination was the most sensitive indicator of malaria infection at delivery. Microscopically detected parasitaemia was associated with increased risk of maternal anaemia at delivery, but not low-grade parasitaemia detected by placental histology only.</p

Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola

<p>Abstract</p> <p>Background</p> <p>Malaria is the infectious disease causing the highest morbidity and mortality in Angola and due to widespread chloroquine (CQ) resistance, the country has recently changed its first-line treatment recommendations for uncomplicated malaria, from CQ to artemisinin combination therapies (ACT) in adults, and sulphadoxine/pyrimethamine (S/P) in pregnant women. Loss of SP sensitivity is, however, progressing rapidly in Africa and, in this study, were investigated a number of molecular markers associated to CQ and S/P.</p> <p>Methods</p> <p>Blood samples were collected from 245 children with uncomplicated malaria, admitted at the Pediatric Hospital Dr. David Bernardino (HPDB), Angola, and the occurrence of mutations in <it>Plasmodium falciparum </it>was investigated in the <it>pfmdr1 </it>(N86Y) and <it>pfcrt </it>(K76T) genes, associated with CQ resistance, as well as in <it>pfdhfr </it>(C59R) and <it>pfdhps </it>(K540E), conferring SP resistance.</p> <p>Results</p> <p>The frequencies of <it>pfmdr1 </it>mutations in codon 86 were 28.6% N, 61.3% Y and 10.1% mixed infections (NY). The frequency of <it>pfcrt </it>mutations in codon 76 were 93.9% K, 5.7% T and 0.4% mixed infections (KT). For <it>pfdhfr </it>the results were in codon 59, 60.6% C, 20.6% R and 18.8% mixed infections (CR). Concerning <it>pfdhps</it>, 6.3% of the isolates were bearers of the mutation 540E and 5.4% mixed infections (K540E).</p> <p>Conclusion</p> <p>The results of this epidemiologic study showed high presence of CQ resistance markers while for SP a much lower prevalence was detected for the markers under study.</p

Intermittent Screening and Treatment versus Intermittent Preventive Treatment of Malaria in Pregnancy: A Randomised Controlled Non-Inferiority Trial

BACKGROUND: The effectiveness of intermittent preventive treatment of malaria in pregnancy (IPTp) may be compromised by the spread of resistance to sulphadoxine/pyrimethamine (SP) across Africa. But little information exists on alternative drugs for IPTp or alternative strategies for the prevention of malaria in pregnancy. Therefore, we have investigated whether screening with a rapid diagnostic test and treatment of those who are positive (IST) at routine antenatal clinic attendances is as effective and as safe as SP-IPTp in pregnant women. METHODS AND FINDINGS: During antenatal clinic sessions in six health facilities in Ghana held between March 2007 and September 2007, 3333 pregnant women who satisfied inclusion criteria were randomised into three intervention arms (1) standard SP-IPTp, (2) IST and treatment with SP or (3) IST and treatment with amodiaquine+artesunate (AQ+AS). All women received a long-lasting insecticide treated net. Study women had a maximum of three scheduled follow-up visits following enrollment. Haemoglobin concentration and peripheral parasitaemia were assessed between 36 and 40 weeks of gestation. Birth weight was measured at delivery or within 72 hours for babies delivered at home. Parasite prevalence at enrollment in primigravidae and in multigravidae was 29.6% and 10.2% respectively. At 36-40 weeks of gestation the prevalence of asymptomatic parasitaemia was 12.1% in study women overall and was very similar in all treatment groups. The risk of third trimester severe anaemia or low birth weight did not differ significantly between the three treatment groups regardless of gravidity. IST with AQ+AS or SP was not inferior to SP-IPTp in reducing the risk of low birth weight (RD  =  -1.17[95%CI; -4.39-1.02] for IST-SP vs. SP-IPTp and RD = 0.78[95%CI; -2.11-3.68] for IST-AQAS vs. SP-IPTp); third trimester severe anaemia (RD = 0.29[95%CI; -0.69-1.30] for IST-SP vs. SP-IPTp and RD  =  -0.36[95%CI;-1.12-0.44] for IST-AQAS vs. SP-IPTp). CONCLUSION: The results of this study suggest that in an area of moderately high malaria transmission, IST with SP or AS+AQ may be a safe and effective strategy for the control of malaria in pregnancy. However, it is important that these encouraging findings are confirmed in other geographical areas and that the impact of IST on placental malaria is investigated. TRIAL REGISTRATION: ClinicalTrials.gov NCT00432367 [NCT00432367]