Submicroscopic Gametocytes and the Transmission of Antifolate-Resistant Plasmodium falciparum in Western Kenya

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up. CONCLUSIONS/SIGNIFICANCE: In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites

Influence of Stimulant Medication and Response Speed on Lateralization of Movement-Related Potentials in Attention-Deficit/Hyperactivity Disorder

Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes.A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology

A 'snip' in time: what is the best age to circumcise?

<p>Abstract</p> <p>Background</p> <p>Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves.</p> <p>Discussion</p> <p>We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used.</p> <p>Summary</p> <p>Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.</p

Public policy, health system, and community actions against illness as platforms for response to NCDs in Tanzania: a narrative review

This review was supported by grants from the Netherlands Organization for International Co-operation in Higher Education and the Ifakara Health Institute, Tanzania

Aircraft icing research flights in embedded convection

Results from in-cloud measurements with an instrumented ircraft from an icing research campaign in Southern Germany in March 1997 are presented. Measurements with conventional optical cloud probes and of the ice accretion on a cylinder exposed to the flow show the existence of supercooled large drops (SLD) in the size range up to 300 mm simultaneously with severe icing with ice-accretion rates of up to 3.5mmmin-1. Nearly all periods with icing, including the ones with severe icing, occurred in mixed-phase convective cells embedded in surrounding stratus clouds. The spatial scales of SLD occurrence, respectively severe icing, ranged between several hundred meters and some kilometers and correspond to the length of the transects through the embedded cells. SLD formed through the coalescence process and were found through the whole cloud depth pointing to a source region near cloud top, in line with the arguments of Rauber and Tokay (1991). No indication of icemultiplication by the Hallet-Mossop process was found, despite of the favorable temperatures for that process. Comparisons of the measured amount of accreted ice with the observed cloud-particle size distributions quite surprisingly indicate that ice accretion is mostly caused by 10–30 mm sized drops rather than by SLD. The latter, therefore, appear to be a by-product of a hypothesized liquid water accumulation zone near cloud top which is also the primary cause of the observed severe ice accretion. The results confirm the importance of embedded convection and of mixed phase clouds with high amounts of liquid water and simultaneously occurring SLD

The potential impact of urine-LAM diagnostics on tuberculosis incidence and mortality: a modelling analysis

Background Lateral flow urine lipoarabinomannan (LAM) tests could offer important new opportunities for the early detection of tuberculosis (TB). The currently licensed LAM test, Alere Determine TB LAM Ag (‘LF-LAM’), performs best in the sickest people living with HIV (PLHIV). However, the technology continues to improve, with newer LAM tests, such as Fujifilm SILVAMP TB LAM (‘SILVAMP-LAM’) showing improved sensitivity, including amongst HIV-negative patients. It is important to anticipate the epidemiological impact that current and future LAM tests may have on TB incidence and mortality. Methods and findings Concentrating on South Africa, we examined the impact that widening LAM test eligibility would have on TB incidence and mortality. We developed a mathematical model of TB transmission to project the impact of LAM tests, distinguishing ‘current’ tests (with sensitivity consistent with LF-LAM), from hypothetical ‘future’ tests (having sensitivity consistent with SILVAMP-LAM). We modelled the impact of both tests, assuming full adoption of the 2019 WHO guidelines for the use of these tests amongst those receiving HIV care. We also simulated the hypothetical deployment of future LAM tests for all people presenting to care with TB symptoms, not restricted to PLHIV. Our model projects that 2,700,000 (95% credible interval [CrI] 2,000,000–3,600,000) and 420,000 (95% CrI 350,000–520,000) cumulative TB incident cases and deaths, respectively, would occur between 2020 and 2035 if the status quo is maintained. Relative to this comparator, current and future LAM tests would respectively avert 54 (95% CrI 33–86) and 90 (95% CrI 55–145) TB deaths amongst inpatients between 2020 and 2035, i.e., reductions of 5% (95% CrI 4%–6%) and 9% (95% CrI 7%–11%) in inpatient TB mortality. This impact in absolute deaths averted doubles if testing is expanded to include outpatients, yet remains <1% of country-level TB deaths. Similar patterns apply to incidence results. However, deploying a future LAM test for all people presenting to care with TB symptoms would avert 470,000 (95% CrI 220,000–870,000) incident TB cases (18% reduction, 95% CrI 9%–29%) and 120,000 (95% CrI 69,000–210,000) deaths (30% reduction, 95% CrI 18%–44%) between 2020 and 2035. Notably, this increase in impact arises largely from diagnosis of TB amongst those with HIV who are not yet in HIV care, and who would thus be ineligible for a LAM test under current guidelines. Qualitatively similar results apply under an alternative comparator assuming expanded use of GeneXpert MTB/RIF (‘Xpert’) for TB diagnosis. Sensitivity analysis demonstrates qualitatively similar results in a setting like Kenya, which also has a generalised HIV epidemic, but a lower burden of HIV/TB coinfection. Amongst limitations of this analysis, we do not address the cost or cost-effectiveness of future tests. Our model neglects drug resistance and focuses on the country-level epidemic, thus ignoring subnational variations in HIV and TB burden. Conclusions These results suggest that LAM tests could have an important effect in averting TB deaths amongst PLHIV with advanced disease. However, achieving population-level impact on the TB epidemic, even in high-HIV-burden settings, will require future LAM tests to have sufficient performance to be deployed more broadly than in HIV care