Changes in the Burden of Malaria Following Scale up of Malaria Control Interventions in Mutasa District, Zimbabwe

Background: To better understand trends in the burden of malaria and their temporal relationship to control activities, a survey was conducted to assess reported cases of malaria and malaria control activities in Mutasa District, Zimbabwe. Methods: Data on reported malaria cases were abstracted from available records at all three district hospitals, three rural hospitals and 25 rural health clinics in Mutasa District from 2003 to 2011. Results: Malaria control interventions were scaled up through the support of the Roll Back Malaria Partnership, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and The President\u27s Malaria Initiative. The recommended first-line treatment regimen changed from chloroquine or a combination of chloroquine plus sulphadoxine/ pyrimethamine to artemisinin-based combination therapy, the latter adopted by 70%, 95% and 100% of health clinics by 2008, 2009 and 2010, respectively. Diagnostic capacity improved, with rapid diagnostic tests (RDTs) available in all health clinics by 2008. Vector control consisted of indoor residual spraying and distribution of longlasting insecticidal nets. The number of reported malaria cases initially increased from levels in 2003 to a peak in 2008 but then declined 39% from 2008 to 2010. The proportion of suspected cases of malaria in older children and adults remained high, ranging from 75% to 80%. From 2008 to 2010, the number of RDT positive cases of malaria decreased 35% but the decrease was greater for children younger than five years of age (60%) compared to older children and adults (26%). Conclusions: The burden of malaria in Mutasa District decreased following the scale up of malaria control interventions. However, the persistent high number of cases in older children and adults highlights the need for strategies to identify locally effective control measures that target all age groups

A Plasmodium-Encoded Cytokine Suppresses T-Cell Immunity During Malaria

The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2-associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs

A multi-transition HCN and HCO+ study of 12 nearby active galaxies: AGN versus SB environments

Recent studies have indicated that the HCN-to-CO(J=1-0) and HCO+-to-HCN(J=1-0) ratios are significantly different between galaxies with AGN (active galactic nucleus) and SB (starburst) signatures. In order to study the molecular gas properties in active galaxies and search for differences between AGN and SB environments, we observed the HCN(J=1-0), (J=2-1), (J=3-2), HCO+(J=1-0) and HCO+(J=3-2), emission with the IRAM 30m in the centre of 12 nearby active galaxies which either exhibit nuclear SB and/or AGN signatures. Consistent with previous results, we find a significant difference of the HCN(J=2-1)-to-HCN(J=1-0), HCN(J=3-2)-to-HCN(J=1-0), HCO+(J=3-2)-to-HCO+(J=3-2), and HCO+-to-HCN intensity ratios between the sources dominated by an AGN and those with an additional or pure central SB: the HCN, HCO+ and HCO+-to-HCN intensity ratios tend to be higher in the galaxies of our sample with a central SB as opposed to the pure AGN cases which show rather low intensity ratios. Based on an LVG analysis of these data, i.e., assuming purely collisional excitation, the (average) molecular gas densities in the SB dominated sources of our sample seem to be systematically higher than in the AGN sources. The LVG analysis seems to further support systematically higher HCN and/or lower HCO+ abundances as well as similar or higher gas temperatures in AGN compared to the SB sources of our sample. Also, we find that the HCN-to-CO ratios decrease with increasing rotational number J for the AGN while they stay mostly constant for the SB sources.Comment: accepted for publication in ApJ; 20 pages, 7 figures; in emulateApJ forma

Cost-Effectiveness of Pre-Exposure Prophylaxis (Prep) in Preventing HIV-1 Infections in Rural Zambia: A Modeling Study

Background: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine effectively prevents new HIV infections. The optimal scenario for implementing PrEP where most infections are averted at the lowest cost is unknown. We determined the impact of different PrEP strategies on averting new infections, prevalence, drug resistance and cost-effectiveness in Macha, a rural setting in Zambia. Methods: A deterministic mathematical model of HIV transmission was constructed using data from the Macha epidemic (antenatal prevalence 7.7%). Antiretroviral therapy is started at CD4/mm 3 . We compared the number of infections averted, cost-effectiveness, and potential emergence of drug resistance of two ends of the prioritization spectrum: prioritizing PrEP to half of the most sexually active individuals (5-15% of the total population), versus randomly putting 40-60% of the total population on PrEP. Results: Prioritizing PrEP to individuals with the highest sexual activity resulted in more infections averted than a non-prioritized strategy over ten years (31% and 23% reduction in new infections respectively), and also a lower HIV prevalence after ten years (5.7%, 6.4% respectively). The strategy was very cost-effective at $323 per quality adjusted life year gained and appeared to be both less costly and more effective than the non-prioritized strategy. The prevalence of drug resistance due to PrEP was as high as 11.6% when all assumed breakthrough infections resulted in resistance, and as low as 1.3% when 10% of breakthrough infections resulted in resistance in both our prioritized and non-prioritized scenarios. Conclusions: Even in settings with low test rates and treatment retention, the use of PrEP can still be a useful strategy in averting infections. Our model has shown that PrEP is a cost-effective strategy for reducing HIV incidence, even when adherence is suboptimal and prioritization is imperfect

A Randomized Controlled Trial of Artemotil (Β-Arteether) in Zambian Children With Cerebral Malaria

The efficacy and safety of intramuscular artemotil (ARTECEF®) was compared to intravenous quinine in African children with cerebral malaria. This prospective block randomized open-label study was conducted at two centers in Zambia. Subjects were children aged 0 to 10 years of age with cerebral malaria and a Blantyre Coma Score of 2 or less. Ninety two children were studied; 48 received artemotil and 44 quinine. No significant differences in survival, coma resolution time, neurologic sequelae, parasite clearance time, and fever resolution time were seen between the two regimens. Rates for negative malaria smears one month after therapy were similar in both groups. Artemotil was a well-tolerated drug in the 48 patients in this study. It appears to be at least therapeutically equivalent to quinine for the treatment of pediatric cerebral malaria. It has the advantage of being able to be given intramuscularly once daily for only five days

SiO chimneys and supershells in M82

In this Letter we present the first images of the emission of SiO and H13CO+ in the nucleus of the starburst galaxy M82. Contrary to other molecular species that mainly trace the distribution of the star-forming molecular gas within the disk, the SiO emission extends noticeably out of the galaxy plane. The bulk of the SiO emission is restricted to two major features. The first feature, referred to as the SiO supershell, is an open shell of 150 pc diameter, located 120 pc west from the galaxy center. The SiO supershell represents the inner front of a molecular shell expanding at 40 km/s, produced by mass ejection around a supercluster of young stars containing supernova remnant SNR 41.95+57.5. The second feature is a vertical filament, referred to as the SiO chimney, emanating from the disk at 200 pc east from the galaxy center. The SiO chimney reaches a 500 pc vertical height, and it is associated with the most prominent chimney identified in radio continuum maps. The kinematics, morphology, and fractional abundances of the SiO gas features in M82 can be explained in the framework of shocked chemistry driven by local episodes of gas ejection from the starburst disk.Comment: 10 pages, 2 figures, published in ApJLetters, 200

A Census of the High-Density Molecular Gas in M82

We present a three-pointing study of the molecular gas in the starburst nucleus of M82 based on 190 - 307 GHz spectra obtained with Z-Spec at the Caltech Submillimeter Observatory. We present intensity measurements, detections and upper limits, for 20 transitions, including several new detections of CS, HNC, C2H, H2CO, and CH3CCH lines. We combine our measurements with previously-published measurements at other frequencies for HCN, HNC, CS, C34S, and HCO+ in a multi-species likelihood analysis constraining gas mass, density and temperature, and the species' relative abundances. We find some 1.7 - 2.7 x 10^8 M_sun of gas with n_H2 between 1 - 6 x 10^4 cm^-3 and T > 50 K. While the mass and temperature are comparable to values inferred from mid-J CO transitions, the thermal pressure is a factor of 10 - 20 greater. The molecular interstellar medium is largely fragmented and is subject to ultraviolet irradiation from the star clusters. It is also likely subject to cosmic rays and mechanical energy input from the supernovae, and is warmer on average than the molecular gas in the massive star formation regions in the Milky Way. The typical conditions in the dense gas in M82's central kpc appear unfavorable for further star formation; if any appreciable stellar populations are currently forming, they are likely biased against low mass stars, producing a top-heavy initial mass function.Comment: 15 pages (using emulateapj.cls), 6 figures, Astrophysical Journal, in pres

Hospitalizations and Costs Incurred at the Facility Level After Scale-Up of Malaria Control: Pre-Post Comparisons From Two Hospitals in Zambia

There is little evidence on the impact of malaria control on the health system, particularly at the facility level. Using retrospective, longitudinal facility-level and patient record data from two hospitals in Zambia, we report a pre-post comparison of hospital admissions and outpatient visits for malaria and estimated costs incurred for malaria admissions before and after malaria control scale-up. The results show a substantial reduction in inpatient admissions and outpatient visits for malaria at both hospitals after the scale-up, and malaria cases accounted for a smaller proportion of total hospital visits over time. Hospital spending on malaria admissions also decreased. In one hospital, malaria accounted for 11% of total hospital spending before large-scale malaria control compared with \u3c 1% after malaria control. The findings demonstrate that facility-level resources are freed up as malaria is controlled, potentially making these resources available for other diseases and conditions

Radio to infrared spectra of late-type galaxies with Planck and WMAP data

We use the Planck Early Release Compact Source Catalogue combined with WMAP and other archival measurements to construct continuum spectra of three nearby dusty star-forming galaxies: Messier 82, NGC 253 and NGC 4945. We carry out a least-squares fit to the spectra using a combination of simple synchrotron, free-free and thermal dust models, and look for evidence of anomalous microwave emission (AME). We find that the radio spectra of all three galaxies are consistent with steep spectrum synchrotron emission, with a significant amount of free-free emission required to explain the Planck and WMAP data points in the frequency range 30-150 GHz. This brings the star-formation rate based on free-free emission into better agreement with that from the non-thermal emission. We place limits on the presence of AME in these galaxies, finding that it is lower than expectations based on the ratio of far infrared to AME from the Galaxy. Nevertheless, the shape of the spectrum of NGC 4945 hints at the presence of AME with a peak around 30 GHz. Future Planck data will let us look more closely at these galaxies, as well as to extend the analysis to many more galaxies.Comment: 5 pages, 1 figure (6 panels), 1 table. Submitted to MNRAS letter

Controlled Release Spatial Repellent Devices (CRDS) as Novel Tools Against Malaria Transmission: A Semi-Field Study in Macha, Zambia

Background: The emergence of mosquitoes that can avoid indoor-deployed interventions, such as treated bed nets and indoor residual spraying, threatens the mainstay of malaria control in Zambia. Furthermore, the requirement for high coverage of these tools poses operational challenges. Spatial repellents are being assessed to supplement these vector control tools, but limitations exist in the residual effect of the repellent and the need for external power or heat for diffusion of the volatiles. Methods: A semi-field evaluation of a novel controlled release spatial repellent device (CRD) was conducted in Macha, Zambia. These devices emanate metofluthrin with no need for external power. Devices were deployed in huts within the semi-field system (SFS). Female Anopheles gambiae sensu stricto released within the SFS were trapped overnight by light traps and collected by aspiration the next morning inside and outside of huts to determine the extent of mosquito repellency and the impact on host-seeking and survival. Experiments studied the impact of number of devices as well as the presence of hut occupants. The study was complemented with numerical methods based on computational fluid dynamics to simulate spatial distribution of metofluthrin. Results: Presence of CRDs was associated with significant reductions in indoor counts of mosquitoes, regardless of whether huts were occupied or not. Repellency ranged from 15 to 60% compared to huts with no devices. Reducing the number of devices from 16 to 4 had little impact on repellency. When huts were occupied, indoor mosquito host-seeking was higher in the presence of CRDs, whilst survival was significantly reduced. Conclusions: This study demonstrated that deployment of as few as four CRDs within a hut was associated with reduced indoor mosquito densities. As would be expected, presence of occupants within huts, resulted in greater indoor catches (both with and without devices). The increased indoor mosquito host-seeking and mortality in huts when devices were present may be explained by the excito-repellency activity of metofluthrin. These semi-field experiments provide preliminary data on the utility of CRD spatial repellents to reduce indoor densities of An. gambiae mosquitoes. Studies will further investigate the impact of CRDs on mosquito behaviour as well as epidemiological protective efficacy