A comparison of the neuroprotective efficacy of newly developed oximes (K117, K127) and currently available oxime (obidoxime) in tabun-poisoned rats

The potency of newly developed bispyridinium compounds (K117, K127) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oxime (obidoxime) using functional observational battery. The neuroprotective effects of atropine alone and atropine combined with one of three bispyridinium oximes (K117, K127, obidoxime) on rats poisoned with tabun at a sublethal dose (180 μg/kg i.m.; 80% of LD50 value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 24 h following tabun challenge while one tabun-poisoned rats died within 24 h after tabun poisoning when the rats were treated with atropine alone. Newly developed oxime K127 combined with atropine was the most effective in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Nevertheless, the differences of neuroprotective efficacy between K127 and obidoxime are not sufficient to replace obidoxime by K127 for the treatment of acute tabun poisonings

Factors associated with prelacteal feeding practices in Debre Berhan district, North Shoa, Central Ethiopia: a cross-sectional, community-based study

Abstract Background Prelacteal feeding is one of the major harmful newborn feeding practices and is top on the list of global public health concerns. The practice deprives newborns of valuable nutrients and protection of colostrum and exposes them to preventable morbidity and mortality. Studying the prevalence and factors influencing the prelacteal feeding practice of mothers will help program managers and implementers to properly address broad major public health problems. Therefore, this study aims to investigate the prevalence of prelacteal feeding practices and its associated factors among mother-infant dyads in the Debre Berhan district of North Shoa administrative zone, central Ethiopia. Methods A community-based cross-sectional study design was conducted from January through to April 2014 among 634 mother-infant dyads. The data were entered into EPI Info version 3.5.1. (CDC, Atlanta, Georgia). All statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) research IBM version 20.0. The prevalence of prelacteal feeding was determined using the ‘recall since birth’ method. Multi-variable logistic regression analysis was employed to control confounders in determining the association between prelacteal feeding practices and selected independent variables. Adjusted Odds Ratio (AOR), with 95% Confidence Interval (CI) and P < 0.05 was used to claim statistical significance. Results The prevalence of prelacteal feeding practice was 14.2% (95% CI: 11.00–17.00%). Slightly greater than half, 48 (53.3%) of prelacteal fed newborns were given butter. Home delivery was a major risk factor for practicing prelacteal feeding. Mothers who delivered their indexed infant at home practiced prelacteal feeding over four folds more than mothers who delivered in a health institution (Adjusted Odds Ratio (AOR) 4.70; 95% CI: 2.56–8.60, p-value = 0.001). Mothers who did not initiate breastfeeding within an hour were six times more likely to practice prelacteal feeding (AOR 5.58; 3.21–9.46, p-value = 0.001). Similarly, with regards to the occupation of mothers, farmers practiced prelacteal feedings (AOR 4.33; 95% CI: 1.73–10.81, p-value = 0.002) up to four folds more than their counterpart housewives. Mothers who can read and write are 54% less likely to practice prelacteal feeding than their counterpart, illiterate mothers, with (AOR 0.46; 95% CI: 0.22–0.98, p-value = 0.044). Conclusions In the Debre Berhan town of North Shoa administrative zone, central Ethiopia, almost one-sixth of mothers practiced prelacteal feeding. Therefore, improving access to information about appropriate newborn feeding practices, encouraging mothers to deliver their babies in health institutions and inspiring them to initiate breastfeeding within an hour of birth is recommended

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Adherence of healthcare providers to malaria case management guidelines of the formal private sector in north-western Ethiopia: an implication for malaria control and elimination

Abstract Background Malaria is an infectious disease which has been globally targeted for elimination in at least 35 of 90 endemic countries by 2030. Most successful malaria elimination country programmes have engaged the private health sector in an effort to identify, document, investigate, provide effective treatment, and follow-up cases. However, there has been limited rigorous research showing evidence of adherence among healthcare providers of the formal private health sector to national malaria diagnosis and treatment guidelines in Ethiopia, starting from malaria control to elimination phases. The aims of this study were to investigate and explain the level of adherence to malaria diagnosis and treatment guidelines among healthcare providers working in formal private health facilities in north-western Ethiopia. Methods An explanatory sequential mixed method design was conducted in the West Gojjam Zone of Ethiopia. Quantitative data were extracted from 1650 medical records of adult uncomplicated malaria outpatients served in 11 private-for-profit health facilities. In addition, using a qualitative approach, 33 in-depth interviews (IDIs) with healthcare providers were conducted. All interviews were audio-recorded, transcribed verbatim, and analysed using eight steps. Results Of 1650 suspected malaria cases in adult outpatients, 80.6% (1330/1650) were screen tested using microscopy and the remainder 19.4% (320/1650) were tested using multispecies rapid diagnosis tests (RDTs). Hence, the results revealed that private healthcare providers universally adhered to diagnosis guidelines. In addition, after following-up and excluding other causes of fever, 4.1% (56/1376) patients were clinically diagnosed with uncomplicated malaria. Despite this, the proportion of private healthcare provider adherence with confirmed malaria case treatment guidelines was 20.9% (69/330). In addition, 1320 (95.9%) of adult outpatients with negative laboratory results were not treated. Some of the identified determinant factors for sub-optimal adherence of healthcare providers to malaria guidelines were interruptions in supply and lack of availability of recommended anti-malarial drugs, lack of availability of quality assured laboratory supplies, and poor knowledge of the recommendations of the national standards. Conclusions Private healthcare providers adhered to universal parasitological diagnosis, providing comprehensive counseling, and linking patients with community health workers. In addition, almost all laboratory negative patients were not treated with anti-malarial drugs. However, only one-fifth of confirmed patients were treated in line with national guideline recommendations. Malaria control and elimination efforts across Ethiopia could be improved through establishing a collaborative function of a win-win public private mix partnership model. In addition, including the data of the private health sector in the health information system could show real malaria burden and use the information to improve the adherence to malaria diagnosis, treatment, and reporting standards within the targeted era of elimination. Therefore, building the capacity of private healthcare providers and ensuring the availability of all nationally recommended drugs and supplies in private health sector facilities is recommended to improve the quality of services

In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Central Ethiopia

<p>Abstract</p> <p>Background</p> <p><it>In vivo </it>efficacy assessments of the first-line treatments for <it>Plasmodium falciparum </it>malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated <it>P. falciparum </it>malaria since 2004.</p> <p>Methods</p> <p>Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for <it>P. falciparum </it>in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented <it>P. falciparum </it>mono-infection were enrolled and followed according to the standard 2009 World Health Organization <it>in vivo </it>drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively.</p> <p>Results</p> <p>Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight <it>P. falciparum </it>patients (6.7%) presented with <it>Plasmodium vivax </it>infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events.</p> <p>Conclusions</p> <p>AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with <it>P. vivax </it>possibly from relapse or new infection was observed.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01052584">NCT01052584</a></p

Sustainable peeling of Kapok Tree (Ceiba pentandra) bark by the chimpanzees (Pan troglodytes verus) of Comoé National Park, Ivory Coast

Primates often consume either bark or cambium (inner bark) as a fallback food to complete their diet during periods of food scarcity. Wild chimpanzees exhibit great behavioral diversity across Africa, as studies of new populations frequently reveal. Since 2014, we have been using a combination of camera traps and indirect signs to study the ecology and behavior of wild chimpanzees (Pan troglodytes verus) in Comoé National Park, Ivory Coast, to document and understand the behavioral adaptations that help them to survive in a savanna–forest mosaic landscape. We found that Comoé chimpanzees peel the bark of the buttresses of kapok tree (Ceiba pentandra) trees to eat the cambium underneath. Individuals of all sex/age classes across at least six neighboring communities peeled the bark, but only during the late rainy season and beginning of the dry season, when cambium may represent an important fallback food. Baboons (Papio anubis) also target the same trees but mainly eat the bark itself. Most of the bark-peeling wounds on Ceiba trees healed completely within 2 years, seemingly without any permanent damage. We recorded chimpanzees visiting trees in early stages of wound recovery but leaving them unpeeled. Only 6% of peeled trees (N = 53) were reexploited after a year, suggesting that chimpanzees waited for the rest of the trees to regrow the bark fully before peeling them again, thus using them sustainably. Many human groups of hunter-gatherers and herders exploited cambium sustainably in the past. The observation that similar sustainable bark-peeling behavior evolved in both chimpanzees and humans suggests that it has an important adaptive value in harsh environments when other food sources become seasonally scarce, by avoiding the depletion of the resource and keeping it available for periods of scarcity