Community-directed distributors—The “foot soldiers” in the fight to control and eliminate neglected tropical diseases

The neglected tropical diseases (NTDs) affect hundreds of millions of people, predominantly in rural, often difficult-to-access areas, poorly served by national health services. Here, we review the contributions of 4.8 million community-directed distributors (CDDs) of medicines over 2 decades in 146,000 communities in 27 sub-Saharan African countries to control or eliminate onchocerciasis and lymphatic filariasis (LF). We examine their role in the control of other NTDs, malaria, HIV/AIDS interventions, immunisation campaigns, and support to overstretched health service personnel. We are of the opinion that CDDs as community selected, trained, and experienced “foot soldiers,” some of whom were involved in the Ebola outbreak responses at the community level in Liberia, if retrained, can assist community leaders and support health workers (HWs) in the ongoing Coronavirus Disease 2019 (COVID-19) crisis. The review highlights the improved treatment coverage where there are women CDDs, the benefits and lessons from the work of CDDs, their long-term engagement, and the challenges they face in healthcare delivery. It underscores the value of utilising the CDD model for strong community engagement and recommends the model, with some review, to hasten the achievement of the NTD 2030 goal and assist the health system cope with evolving epidemics and other challenges. We propose that, based on the unprecedented progress made in the control of NTDs directly linked to community engagement and contributions of CDDs “foot soldiers,” they deserve regional and global recognition. We also suggest that the World Health Organization (WHO) and other international stakeholders promote policy and guidance for countries to adapt this model for the elimination of NTDs and to strengthen national health services. This will enhance the accomplishment of some Sustainable Development Goals (SDGs) by 2030 in sub-Saharan Africa.     

Inhibition of DNA replication by berenil in plasmids containing Poly(dA)poly(dT) sequences

The effect of berenil on plasmid DNA replication was studied on pBR322-derived plasmids containing poly(dA)poly(dT) sequences. In comparison to the parental plasmid pBR322, plasmid pKH47 harboring 100 bp of poly(dA)poly(dT) at the PvuII site showed a decrease in plasmid yield in the presence of berenil. This effect was also observed in pVL26, a related plasmid in which the location of the poly(dA)poly(dT) region had been shifted to the EcoRV site in pBR322. [(3)H]Thymidine incorporation experiments indicated that DNA synthesis may be affected in these plasmids in the presence of the drug. Bromodeoxyuridine incorporation experiments coupled to Cs(2)SO(4) equilibrium density gradient centrifugation indicated that the lower plasmid yield was due to an inhibition of DNA replication by berenil. We have also found that berenil induces DNA degradation in plasmids containing the homopolymer. Our studies strongly suggest that the effect of berenil on plasmid replication and DNA stability results from its binding to the poly(dA)poly(dT) region present in these plasmids. Moreover, we have found a correlation between the position of the poly(dA)poly(dT) region and this inhibitory effect. Thus, plasmid pKH47, containing the poly(dA)poly(dT) region most proximal to the origin of pBR322 replication, was most severely affected.     

Morinda lucida reduces contractility of isolated uterine smooth muscle of pregnant and non-pregnant mice.

The present work investigated the effect of Morinda lucida (M. lucida) extract on isolated uterine smooth muscle of pregnant and non-pregnant mice. Pregnant and non-pregnant mice were pretreated with oral stilboesterol (0.1 mg/kg body weight) and killed by cervical dislocation. Thin strips of the uterus were cut and mounted in a 20ml organ bath containing De Jalon solution bubbled with 95%O2-5% CO2 gas mixture. The strips were connected to a force transducer coupled to a Grass 7D Polygraph for the recording of isometric tension. Effects of graded concentrations of oxytocin (OXY; 10-5-10-2 mol/L), acetylcholine (ACh; 10-9-10-5 mol/L) and M. lucida extract (0.015-1.5 mg/ml) were recorded. Fresh uterine strips were then incubated with M. lucida extract for 5mins and cumulative response to OXY was repeated. Another set of fresh strips was incubated in L-NAME for 15mins and the cumulative responses to M.lucida extract were repeated. OXY resulted in increased contractile responses in both pregnant and non-pregnant uterine muscles. M. lucida resulted in relaxation of the uterine smooth muscle in both pregnant and non-pregnant mice at all doses. However, at 1.5mg/ml, M. lucida completely blocked spontaneous uterine contractions. Following incubation with L-NAME, M. lucida extract led to a slightly greater relaxation of the uterine strips. In conclusion, M. lucida reduced contractility of uterine smooth muscle in both pregnant and non-pregnant mice as well as blocking contractile responses to OXY and Ach in uterine smooth muscle of pregnant and non-pregnant mice. There was no significant alteration of M. lucida activity by L-NAME suggesting that the action of the compound on uterine muscle is not associated with impaired nitric oxide synthase.     

Enhancing learning objectives by use of simple virtual microscopic slides in cellular physiology and histology: impact and attitudes

The impact and perception of students on the use of a simple, low technology-driven version of a virtual microscope in teaching and assessments in cellular physiology and histology were studied. Its impact on the time and resources of the faculty were also assessed. Simple virtual slides and conventional microscopes were used to conduct the same examinations for the same students. Students performed significantly better in the examination with the virtual slide and also showed a significantly higher preference for virtual slides. The time and cost implications of conducting examinations using the simple virtual slides were reduced by >1,400%. The results reemphasize the need for the design and adoption of simple sustainable technological innovations in developing countries to bridge gaps in purposeful learning environments.     

Assessment of the Quality of Antenatal Care Services Provided by Health Workers Using a Mobile Phone Decision Support Application in Northern Nigeria: A Pre/Post-Intervention Study

BackgroundGiven the shortage of skilled healthcare providers in Nigeria, frontline community health extension workers (CHEWs) are commonly tasked with providing maternal and child health services at primary health centers. In 2012, we introduced a mobile case management and decision support application in twenty primary health centers in northern Nigeria, and conducted a pre-test/post-test study to assess whether the introduction of the app had an effect on the quality of antenatal care services provided by this lower-level cadre.MethodsUsing the CommCare mobile platform, the app dynamically guides CHEWs through antenatal care protocols and collects client data in real time. Thirteen health education audio clips are also embedded in the app for improving and standardizing client counseling. To detect changes in quality, we developed an evidence-based quality score consisting of 25 indicators, and conducted a total of 266 client exit interviews. We analyzed baseline and endline data to assess changes in the overall quality score as well as changes in the provision of key elements of antenatal care.ResultsOverall, the quality score increased from 13.3 at baseline to 17.2 at endline (p<0.0001), out of a total possible score of 25, with the most significant improvements related to health counseling, technical services provided, and quality of health education.ConclusionThese study results suggest that the introduction of a low-cost mobile case management and decision support application can spur behavior change and improve the quality of services provided by a lower level cadre of healthcare workers. Future research should employ a more rigorous experimental design to explore potential longer-term effects on client health outcomes.     

A unique deletion in pBR322 DNA caused by insertion of poly(dA) · poly(dT)

A unique deletion covering around 43% of the pBR322 genome was found after attempting to insert 100 or 200 bp poly(dA) · poly(dT) into the EcoRV site of pBR322 DNA. This result was not observed if an equivalent size heterologous DNA or a larger poly(dA) · poly(dT) fragment of 10–20,000 bp was introduced at the same site. DNA sequencing analysis at the junctions suggests that a specific intramolecular pairing may be involved in the formation of this deletion mutant.     

Bayesian Geostatistical Model-Based Estimates of Soil-Transmitted Helminth Infection in Nigeria,Including Annual Deworming Requirements

Background

The acceleration of the control of soil-transmitted helminth (STH) infections in Nigeria, emphasizing preventive chemotherapy, has become imperative in light of the global fight against neglected tropical diseases. Predictive risk maps are an important tool to guide and support control activities.

Methodology

STH infection prevalence data were obtained from surveys carried out in 2011 using standard protocols. Data were geo-referenced and collated in a nationwide, geographic information system database. Bayesian geostatistical models with remotely sensed environmental covariates and variable selection procedures were utilized to predict the spatial distribution of STH infections in Nigeria.

Principal Findings

We found that hookworm, Ascaris lumbricoides, and Trichuris trichiura infections are endemic in 482 (86.8%), 305 (55.0%), and 55 (9.9%) locations, respectively. Hookworm and A. lumbricoides infection co-exist in 16 states, while the three species are co-endemic in 12 states. Overall, STHs are endemic in 20 of the 36 states of Nigeria, including the Federal Capital Territory of Abuja. The observed prevalence at endemic locations ranged from 1.7% to 51.7% for hookworm, from 1.6% to 77.8% for A. lumbricoides, and from 1.0% to 25.5% for T. trichiura. Model-based predictions ranged from 0.7% to 51.0% for hookworm, from 0.1% to 82.6% for A. lumbricoides, and from 0.0% to 18.5% for T. trichiura. Our models suggest that day land surface temperature and dense vegetation are important predictors of the spatial distribution of STH infection in Nigeria. In 2011, a total of 5.7 million (13.8%) school-aged children were predicted to be infected with STHs in Nigeria. Mass treatment at the local government area level for annual or bi-annual treatment of the school-aged population in Nigeria in 2011, based on World Health Organization prevalence thresholds, were estimated at 10.2 million tablets.

Conclusions/Significance

The predictive risk maps and estimated deworming needs presented here will be helpful for escalating the control and spatial targeting of interventions against STH infections in Nigeria.     

Inflammatory-induced hibernation in the fetus: priming of fetal sheep metabolism correlates with developmental brain injury

Prenatal inflammation is considered an important factor contributing to preterm birth and neonatal mortality and morbidity. The impact of prenatal inflammation on fetal bioenergetic status and the correlation of specific metabolites to inflammatory-induced developmental brain injury are unknown. We used a global metabolomics approach to examine plasma metabolites differentially regulated by intrauterine inflammation. Preterm-equivalent sheep fetuses were randomized to i.v. bolus infusion of either saline-vehicle or LPS. Blood samples were collected at baseline 2 h, 6 h and daily up to 10 days for metabolite quantification. Animals were killed at 10 days after LPS injection, and brain injury was assessed by histopathology. We detected both acute and delayed effects of LPS on fetal metabolism, with a long-term down-regulation of fetal energy metabolism. Within the first 3 days after LPS, 121 metabolites were up-regulated or down-regulated. A transient phase (4-6 days), in which metabolite levels recovered to baseline, was followed by a second phase marked by an opposing down-regulation of energy metabolites, increased pO(2) and increased markers of inflammation and ADMA. The characteristics of the metabolite response to LPS in these two phases, defined as 2 h to 2 days and at 6-9 days, respectively, were strongly correlated with white and grey matter volumes at 10 days recovery. Based on these results we propose a novel concept of inflammatory-induced hibernation of the fetus. Inflammatory priming of fetal metabolism correlated with measures of brain injury, suggesting potential for future biomarker research and the identification of therapeutic targets.