Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance

Trypanosoma brucei rhodesiense (Tbr) and T. b. gambiense (Tbg), causative agents of Human African Trypanosomiasis (sleeping sickness) in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs), components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA) protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR). HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb), a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1) and not found in related taxa, which are either human serum susceptible (Tbb) or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2). We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR functio

How does Trypanosoma equiperdum fit into the Trypanozoon group? A cluster analysis by RAPD and multiplex-endonuclease genotyping approach.

The pathogenic trypanosomes Trypanosoma equiperdum, T. evansi as well as T. brucei are morphologically identical. In horses, these parasites are considered to cause respectively dourine, surra and nagana. Previous molecular attempts to differentiate these species were not successful for T. evansi and T. equiperdum; only T. b. brucei could be differentiated to a certain extent. In this study we analysed 10 T. equiperdum, 8 T. evansi and 4 T. b. brucei using Random Amplified Polymorphic DNA (RAPD) and multiplex-endonuclease fingerprinting, a modified AFLP technique. The results obtained confirm the homogeneity of the T. evansi group tested. The T. b. brucei clustered out in a heterogenous group. For T. equiperdum the situation is more complex: 8 out of 10 T. equiperdum clustered together with the T. evansi group, while 2 T. equiperdum strains were more related to T. b. brucei. Hence, 2 hypotheses can be formulated: (1) only 2 T. equiperdum strains are genuine T. equiperdum causing dourine; all other T. equiperdum strains actually are T. evansi causing surra or (2) T. equiperdum does not exist at all. In that case, the different clinical outcome of horse infections with T. evansi or T. b. brucei is primarily related to the host immune response

Persistent hypertension up to one year postpartum among women with hypertensive disorders in pregnancy in a low-resource setting:A prospective cohort study

BACKGROUND: Hypertensive disorders in pregnancy (HDPs) are associated with lifelong cardiovascular disease risk. Persistent postpartum hypertension in HDPs could suggest progression to chronic hypertension. This phenomenon has not been well examined in low- and middle-income countries (LIMCs), and most previous follow-ups typically last for maximally six weeks postpartum. We assessed the prevalence of persistent hypertension up to one year in women with HDPs in a low resource setting and determined associated risk factors. METHODOLOGY: A prospective cohort study of women conducted at eight tertiary health care facilities in seven states of Nigeria. Four hundred and ten women with any HDP were enrolled within 24 hours of delivery and followed up at intervals until one year postpartum. Descriptive statistics were performed to express the participants’ characteristics. Univariable and multivariable logistic regressions were conducted to identify associated risk factors. RESULTS: Of the 410 women enrolled, 278 were followed up to one year after delivery (follow-up rate 68%). Among women diagnosed with gestational hypertension and pre-eclampsia/eclampsia, 22.3% (95% CI; 8.3–36.3) and 62.1% (95% CI; 52.5–71.9), respectively, had persistent hypertension at six months and this remained similar at one year 22.3% (95% CI; 5.6–54.4) and 61.2% (95% CI; 40.6–77.8). Maternal age and body mass index were significant risk factors for persistent hypertension at one year [aORs = 1.07/year (95% CI; 1.02–1.13) and 1.06/kg/m(2) (95% CI; 1.01–1.10)], respectively. CONCLUSION: This study showed a substantial prevalence of persistent hypertension beyond puerperium. Health systems in LMICs need to be organized to anticipate and maintain postpartum monitoring until blood pressure is normalized, or women referred or discharged to family physicians as appropriate. In particular, attention should be given to women who are obese, and or of higher maternal age

Metabolic syndrome following hypertensive disorders in pregnancy in a low-resource setting:A cohort study

Objectives: Hypertensive disorders in pregnancy (HDPs) are associated with risk of future metabolic syndrome. Despite the huge burden of HDPs in sub-Saharan Africa, this association has not been adequately studied in this population. Study design: This was a prospective cohort study on pregnant women recruited between August 2017 - April 2018 and followed up to one year after their deliveries and evaluated for presence of metabolic syndrome at delivery, nine weeks, six months and one year. Main outcome measures: Prevalence of metabolic syndrome Results: A total of 488 pregnant women were included: 410 and 78 with HDPs and normotensive, respectively. None of the normotensive had metabolic syndrome until one year (1.7% = 1 out of 59 observations), while among those with HDPs were 17.4% (71 of 407), 8.7% (23 of 263), 4.7% (11 of 232) and 6.1% (17 of 278), at delivery, nine weeks, six months and one year postpartum, respectively. High BMI and blood pressure were the drivers of metabolic syndrome in this population. The incidence rate in HDPs versus normotensive at one year were, respectively, 57.5/1000 persons’ year (95%CI; 35.8 – 92.6) and 16.9/1000 persons’ years (95%CI; 2.4-118.3), with incidence rate ratio of 3.4/1000 person's years. Only parity significantly predicted the presence of metabolic syndrome at one year [(aOR= 3.26/delivery (95%CI; 1.21-8.79)]. Conclusion: HDPs were associated with a higher incidence of metabolic syndrome up to one year postpartum. Women with HDPs should be routinely screened for metabolic syndrome within the first year postpartum to reduce cardiometabolic risks.</p

Impact of three years of large scale Indoor Residual Spraying (IRS) and Insecticide Treated Nets (ITNs) interventions on insecticide resistance in Anopheles gambiae s.l. in Benin

<p>Abstract</p> <p>Background</p> <p>In Benin, Indoor Residual Spraying (IRS) and long-lasting insecticidal nets (LLINs) are the cornerstones of malaria prevention. In the context of high resistance of <it>Anopheles gambiae </it>to pyrethroids, The National Malaria Control Program (NMCP) has undertaken a full coverage of IRS in a no-flood zone in the Oueme region, coupled with the distribution of LLINs in a flood zone. We assessed the impact of this campaign on phenotypic resistance, <it>kdr </it>(knock-down resistance) and <it>ace-1^R</it>(insensitive acetylcholinesterase) mutations.</p> <p>Methods</p> <p>Insecticides used for malaria vector control interventions were bendiocarb WP (0.4 g/m²) and deltamethrin (55 mg/m²), respectively for IRS and LLINs. Susceptibility status of <it>An. gambiae </it>was assessed using World Health Organization bioassay tests to DDT, permethrin, deltamethrin and bendiocarb in the Oueme region before intervention (2007) and after interventions in 2008 and 2010. <it>An. gambiae </it>specimens were screened for identification of species, molecular M and S forms and for the detection of the West African <it>kdr </it>(L1014F) as well as <it>ace-1^R</it>mutations using PCR techniques.</p> <p>Results</p> <p>The univariate logistic regression performed showed that <it>kdr </it>frequency has increased significantly during the three years in the intervention area and in the control area. Several factors (LLINs, IRS, mosquito coils, aerosols, use of pesticides for crop protection) could explain the selection of individual resistant <it>An. gambiae</it>. The <it>Kdr </it>resistance gene could not be the only mechanism of resistance observed in the Oueme region. The high susceptibility to bendiocarb is in agreement with a previous study conducted in Benin. However, the occurrence of <it>ace-1^R</it>heterozygous individuals even on sites far from IRS areas, suggests other factors may contribute to the selection of resistance other than those exerted by the vector control program.</p> <p>Conclusion</p> <p>The results of this study have confirmed that <it>An.gambiae </it>have maintained and developed the resistance to pyrethroids, but are still susceptible to bendiocarb. Our data clearly shows that selection of resistant individuals was caused by other insecticides than those used by the IRS and LLINs.</p