Use of wind-up fetal Doppler versus Pinard for fetal heart rate intermittent monitoring in labour: a randomised clinical trial.

OBJECTIVES: In resource-poor settings, the standard of care to inform labour management is the partograph plus Pinard stethoscope for intermittent fetal heart rate (FHR) monitoring. We compared FHR monitoring in labour using a novel, robust wind-up handheld Doppler with the Pinard as a primary screening tool for abnormal FHR on perinatal outcomes. DESIGN: Prospective equally randomised clinical trial. SETTING: The labour and delivery unit of a teaching hospital in Kampala, Uganda. PARTICIPANTS: Of the 2042 eligible antenatal women, 1971 women in active term labour, following uncomplicated pregnancies, were randomised to either the standard of care or not. INTERVENTION: Intermittent FHR monitoring using Doppler. PRIMARY OUTCOME MEASURES: Incidence of FHR abnormality detection, intrapartum stillbirth and neonatal mortality prior to discharge. RESULTS: Age, parity, gestational age, mode of delivery and newborn weight were similar between study groups. In the Doppler group, there was a significantly higher rate of FHR abnormalities detected (incidence rate ratio (IRR)=1.61, 95% CI 1.13 to 2.30). However, in this group, there were also higher though not statistically significant rates of intrapartum stillbirths (IRR=3.94, 0.44 to 35.24) and neonatal deaths (IRR=1.38, 0.44 to 4.34). CONCLUSIONS: Routine monitoring with a handheld Doppler increased the identification of FHR abnormalities in labour; however, our trial did not find evidence that this leads to a decrease in the incidence of intrapartum stillbirth or neonatal death. TRIAL REGISTRATION NUMBER: Clinical Trails.gov (1000031587)

PROPERTIES OF EXTRUDATES FROM SORGHUM VARIETIES

Extrusion cooking is a modern high-temperature short-time (HTST) processing technology, which is becoming popular in certain industries because it offers several advantages over other types of cooking processes. The objective of this study was to evaluate the extrusion performance of sorghum ( Sorghum bicolor ) varieties commonly grown in Uganda. Four varieties of sorghum namely, Seso1, Epuripur, Seso3 and Eyera were extruded with and without defatted soy-flour. Physical-chemical properties of the extrudates including, lateral expansion, bulk density, hardness, water absorption index, water solubility index, as well as proximate composition were determined. The extrudates exhibited 240-300% lateral expansion and 0.067-0.095 g cm-3 bulk density. The water absorption index was 6.4-7.9 g g-1 compared to 1.9-2.3 g g-1 of the control; while the water solubility index was 6.5-13% compared to 3.4-5.0% of the control. Extrusion of all the varieties reduced the peak and final viscosity of the extrudates. There were no varietal differences with respect to lateral expansion, bulk density and hardness. However, the water absorption index for the varieties increased in the order, Eyera, Seso 3, Seso 1 and Epuripur; while the water solubility index for the varieties increased in the order, Seso 1, Seso 3, Eyera and Epuripur. Defatted soybean flour had no effect on the extrudate properties. The results suggest that the four sorghum varieties in this study can be used in the production of extruded puffed snacks, breakfast cereals and other food products.La cuisson-extrusion est une technologie moderne de cuisson rapide \ue0 haute temp\ue9rature qui devient de plus en plus populaire dans certaines industries parce qu\u2019elle offre plusieurs avantages face \ue0 d\u2019autres proc\ue9d\ue9s de cuisson. L\u2019objectif de cette \ue9tude \ue9tait d\u2019\ue9valuer la performance de l\u2019extrusion des vari\ue9t\ue9s du sorgho ( Sorghum bicolor ) commun\ue9ment cultiv\ue9es en Ouganda. Quatre vari\ue9t\ue9s du sorgho dont Seso1, Epuripur, Seso3 et Eyera \ue9taient extrud\ue9es avec et sans farine du soja d\ue9graiss\ue9e. Les propri\ue9t\ue9s physico-chimiques de l\u2019extrudant incluant l\u2019expansion lat\ue9rale, la densit\ue9 volumique, la duret\ue9, l\u2019indice d\u2019absorption d\u2019eau ainsi que la composition chimique \ue9taient d\ue9termin\ue9es. Les extrudants ont manifest\ue9 240-300% de l\u2019expansion lat\ue9rale et 0.067-0.095 g cm-3 de la densit\ue9 volumique. L\u2019indice d\u2019absorption d\u2019eau \ue9tait de 6.4-7.9 g g-1 en comparaison avec 1.9-2.3 g g-1 dans le contr\uf4le, pendant que l\u2019indice de solubilit\ue9 dans l\u2019eau \ue9tait de 6.5-13% contre 3.4-5.0% dans le contr\uf4le. L\u2019extrusion de toute les vari\ue9t\ue9s a r\ue9duit l\u2019apog\ue9e et la viscosit\ue9 finale des extrudants. Il n\u2019y avait pas de diff\ue9rences significatives entre les vari\ue9t\ue9s au niveau de l\u2019expansion lat\ue9rale, la densit\ue9 volumique et la duret\ue9. Par ailleurs, l\u2019indice d\u2019absorption d\u2019eau pour les vari\ue9t\ue9s a augment\ue9 dans l\u2019ordre pour les vari\ue9t\ue9s Eyera, Seso 3, Seso 1 et Epuripur; pendant que l\u2019indice de solubilit\ue9 dans l\u2019eau pour les vari\ue9t\ue9s a augment\ue9 dans l\u2019ordre pour les vari\ue9t\ue9s Seso 1, Seso 3, Eyera et Epuripur. La farine degraiss\ue9e de soja n\u2019avait aucun effet sur les propri\ue9t\ue9s de l\u2019extrudant. Ces r\ue9sultats sugg\ue8rent que toutes les quatre vari\ue9t\ue9s de sorgho dans cette \ue9tude peuvent \ueatre utilis\ue9es dans la production des collations , c\ue9r\ue9ales pour petit d\ue9jeuner et autres produits alimentaires

Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda.

Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children

Drug susceptibility of Plasmodium falciparum in eastern Uganda: a longitudinal phenotypic and genotypic study

Background: Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) and is challenged by drug resistance, but thus far resistance to artemisinins and partner drugs has primarily occurred in southeast Asia. The aim of this study was to characterise antimalarial drug susceptibility of Plasmodium falciparum isolates from Tororo and Busia districts in Uganda. Methods: In this prospective longitudinal study, P falciparum isolates were collected from patients aged 6 months or older presenting at the Tororo District Hospital (Tororo district, a site with relatively low malaria incidence) or Masafu General Hospital (Busia district, a high-incidence site) in eastern Uganda with clinical symptoms of malaria, a positive Giemsa-stained blood film for P falciparum, and no signs of severe disease. Ex-vivo susceptibilities to ten antimalarial drugs were measured using a 72-h microplate growth inhibition assay with SYBR Green detection. Relevant P falciparum genetic polymorphisms were characterised by molecular methods. We compared results with those from earlier studies in this region and searched for associations between drug susceptibility and parasite genotypes. Findings: From June 10, 2016, to July 29, 2019, 361 P falciparum isolates were collected in the Busia district and 79 in the Tororo district from 440 participants. Of 440 total isolates, 392 (89%) successfully grew in culture and showed excellent drug susceptibility for chloroquine (median half-maximal inhibitory concentration [IC50] 20·0 nM [IQR 12·0-26·0]), monodesethylamodiaquine (7·1 nM [4·3-8·9]), pyronaridine (1·1 nM [0·7-2·3]), piperaquine (5·6 nM [3·3-8·6]), ferroquine (1·8 nM [1·5-3·3]), AQ-13 (24·0 nM [17·0-32·0]), lumefantrine (5·1 nM [3·2-7·7]), mefloquine (9·5 nM [6·6-13·0]), dihydroartemisinin (1·5 nM [1·0-2·0]), and atovaquone (0·3 nM [0·2-0·4]). Compared with results from our study in 2010-13, significant improvements in susceptibility were seen for chloroquine (median IC50 288·0 nM [IQR 122·0-607·0]; p\u3c0·0001), monodesethylamodiaquine (76·0 nM [44·0-137]; p\u3c0·0001), and piperaquine (21·0 nM [7·6-43·0]; p\u3c0·0001), a small but significant decrease in susceptibility was seen for lumefantrine (3·0 nM [1·1-7·6]; p\u3c0·0001), and no change in susceptibility was seen with dihydroartemisinin (1·3 nM [0·8-2·5]; p=0·64). Chloroquine resistance (IC50\u3e100 nM) was more common in isolates from the Tororo district (11 [15%] of 71), compared with those from the Busia district (12 [4%] of 320; p=0·0017). We showed significant increases between 2010-12 and 2016-19 in the prevalences of wild-type P falciparum multidrug resistance protein 1 (PfMDR1) Asn86Tyr from 60% (391 of 653) to 99% (418 of 422; p\u3c0·0001), PfMDR1 Asp1246Tyr from 60% (390 of 650) to 90% (371 of 419; p\u3c0·0001), and P falciparum chloroquine resistance transporter (PfCRT) Lys76Thr from 7% (44 of 675) to 87% (364 of 417; p\u3c0·0001). Interpretation: Our results show marked changes in P falciparum drug susceptibility phenotypes and genotypes in Uganda during the past decade. These results suggest that additional changes will be seen over time and continued surveillance of susceptibility to key ACT components is warranted. Funding: National Institutes of Health and Medicines for Malaria Venture

Point-of-admission hypothermia among high-risk Nigerian newborns

<p>Abstract</p> <p>Background</p> <p>Facilities which manage high-risk babies should frequently assess the burden of hypothermia and strive to reduce the incidence.</p> <p>Objective</p> <p>To determine the incidence and outcome of point-of-admission hypothermia among hospitalized babies.</p> <p>Methods</p> <p>The axillary temperatures of consecutive admissions into a Nigerian Newborn Unit were recorded. Temperature <36.5°C defined hypothermia. The biodata and outcome of these babies were studied.</p> <p>Results</p> <p>Of 150 babies aged 0 to 648 hours, 93 had hypothermia with an incidence of 62%. Mild and moderate hypothermia accounted for 47.3% and 52.7% respectively. The incidence of hypothermia was highest (72.4%) among babies aged less than 24 hours. It was also higher among out-born babies compared to in-born babies (64.4% <it>vs </it>58.3%). Preterm babies had significantly higher incidence of hypothermia (82.5%) compared with 54.5% of term babies (RR = 1.51; CI = 1.21 – 1.89). The incidence of hypothermia was also highest (93.3%) among very-low-birth-weight babies.</p> <p>The Case-Fatality-Rate was significantly higher among hypothermic babies (37.6% vs 16.7%; RR = 2.26, CI = 1.14 – 4.48) and among out-born hypothermic babies (50% vs 17.1%; RR = 0.34, CI = 0.16 – 0.74). CFR was highest among hypothermic babies with severe respiratory distress, sepsis, preterm birth and asphyxia.</p> <p>Conclusion</p> <p>The high incidence and poor outcome of hypothermia among high-risk babies is important. The use of the 'warm chain' and skin-to-skin contact between mother and her infant into routine delivery services in health facilities and at home may be useful.</p

Associations between Varied Susceptibilities to PfATP4 Inhibitors and Genotypes in Ugandan Plasmodium falciparum Isolates.

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda, from 2016 to 2019. Median IC50s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many nonsynonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K (16%), and D1116G/N/Y (16%). The G223S mutation was associated with decreased susceptibility to SJ733, PA92, and KAE609. The D1116G/N/Y mutations were associated with decreased susceptibility to SJ733, and the presence of mutations at both codons 223 and 1116 was associated with decreased susceptibility to PA92 and SJ733. In all of these cases, absolute differences in susceptibilities of wild-type (WT) and mutant parasites were modest. Analysis of clones separated from mixed field isolates consistently identified mutant clones as less susceptible than WT. Analysis of isolates from other sites demonstrated the presence of the G223S and D1116G/N/Y mutations across Uganda. Our results indicate that malaria parasites circulating in Uganda have a number of polymorphisms in PfATP4 and that modestly decreased susceptibility to PfATP4 inhibitors is associated with some mutations now present in Ugandan parasites

Impact of Antimalarial Treatment and Chemoprevention on the Drug Sensitivity of Malaria Parasites Isolated from Ugandan Children

Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. Over time, ex vivo sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of pfcrt K76 and pfmdr1 N86 and D1246 increased, and the prevalences of pfdhfr and pfdhps polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased ex vivo lumefantrine sensitivity and increased prevalence of pfcrt K76 and pfmdr1 N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of pfmdr1 86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively

Poor newborn care practices - a population based survey in eastern Uganda

BACKGROUND: Four million neonatal deaths are estimated to occur each year and almost all in low income countries, especially among the poorest. There is a paucity of data on newborn health from sub-Saharan Africa and few studies have assessed inequity in uptake of newborn care practices. We assessed socioeconomic differences in use of newborn care practices in order to inform policy and programming in Uganda. METHODS: All mothers with infants aged 1-4 months (n = 414) in a Demographic Surveillance Site were interviewed. Households were stratified into quintiles of socioeconomic status (SES). Three composite outcomes (good neonatal feeding, good cord care, and optimal thermal care) were created by combining related individual practices from a list of twelve antenatal/essential newborn care practices. Multiple logistic regression analysis was used to identify determinants of each dichotomised composite outcome. RESULTS: There were low levels of coverage of newborn care practices among both the poorest and the least poor. SES and place of birth were not associated with any of the composite newborn care practices. Of newborns, 46% had a facility delivery and only 38% were judged to have had good cord care, 42% optimal thermal care, and 57% were considered to have had adequate neonatal feeding. Mothers were putting powder on the cord; using a bottle to feed the baby; and mixing/replacing breast milk with various substitutes. Multiparous mothers were less likely to have safe cord practices (OR 0.5, CI 0.3 - 0.9) as were mothers whose labour began at night (OR 0.6, CI 0.4 - 0.9). CONCLUSION: Newborn care practices in this setting are low and do not differ much by socioeconomic group. Despite being established policy, most neonatal interventions are not reaching newborns, suggesting a "policy-to-practice gap". To improve newborn survival, newborn care should be integrated into the current maternal and child interventions, and should be implemented at both community and health facility level as part of a universal coverage strategy