Laboratory-confirmed Congenital Rubella Syndrome at the University Teaching Hospital in Lusaka, Zambia-Case Reports

Background: Congenital rubella syndrome (CRS) caused by rubella infection in uterine, is a major public health problem among women of child bearing age as it causes serious complications including foetal death or  abnormalities including cardiovascular, ophthalmologic, respiratory and hearing impairment. Though there is  evidence of rubella infection amongst the population under the expanded programme on immunization (epi)  surveillance programme, there is no documented evidence of laboratory confirmed congenital rubella syndrome  cases in Zambia. A report is given on four cases of CRS that were identified and confirmed during routine activities of the national measles surveillance program in Zambia. Clinical data on the symptomatic cases were collected and  serum samples tested for rubella IgM to confirm the cases.Case presentation: The first confirmed case was a baby girl presented to the Neonatal Intensive Care unit of the University Teaching Hospital for low birth weight and hypothermia. At seven weeks, the girl was found to have  cataracts, spleno-hepatomegaly, microcephaly, and patent ductus arteriosus (PDA). The baby tested positive to  rubella IgM antibodies. The second case was a baby boy who was first seen at the University Teaching Hospital at  three weeks and on examination was found to have bilateral cataracts, congenital heart disease and microcephaly.  Rubella Immunoglobulin M (IgM) results were positive. The third case, a girl, was seen at twelve weeks and brought in for slow growth rate. On examination, the girl was found to have bilateral cataracts,  microcephaly and  developmental delay. The fourth case is a girl who was brought to the hospital for failure to thrive, tachypnea and  fever. On further investigations there was evidence of cataracts, patent ductus arteriosus. At eight weeks, she tested  positive for rubella IgM antibodies.Conclusion: The clinical symptoms and laboratory evidence of rubella infection confirmed congenital rubella syndrome in the four patients. There is an urgent need for surveillance of congenital rubella syndrome and a  baseline rubella sero-prevalence survey in Zambia in order to determine the burden of the disease and use this  data to direct policy in terms of interventions for supportive treatment, control and possible elimination of rubella  infection through immunization with measlesrubella vaccine.Keywords: Congenital Rubella Syndrome; Confirmed; Measles-Rubella vaccine; Lusaka, Zambi

A comparison between three legacy soil maps of Zambia at national scale: The spatial patterns of legend units and their relation to soil properties

We examined three soil maps of Zambia, two published at scales of 1:1 million – the Exploratory Soil Map of Zambia (ESMZ) and the Vegetation–Soil Map produced by Trapnell and colleagues in 1947 – and one at 1:3 million, the Soil Atlas of Africa (SAA). We estimated components of variance for measurements of clay, sand and organic carbon content and bulk density of the soil across the country using models which included different mean values for soil map units as random effects. For all but organic carbon content there was significant variation accounted for by differences between legend units for two of the maps, ESMZ with legend units based on the FAO-Unesco and SAA with legend units based on the World Reference Base respectively. This was despite their small cartographic scale. For the Vegetation–Soil Map, we examined differences between broad soil physiographic units. These did not account for significant variation in the soil properties. There were clear similarities between the soil physiographic units of the Soil–Vegetation Map and broader physiographic units into which the legend units of the ESMZ are grouped. The spatial pattern of soil units of the SAA was the most spatially heterogeneous, as measured by the sum of indicator variograms, despite being at the smallest published scale. It was apparent that some of the soil variation within the largest physiographic unit of the Soil–Vegetation Map, the Plateau Soils, as expressed by the map units of the SAA was significantly associated with the different vegetation units mapped in 1947. These studies show how quantitative assessment of legacy soil information may help us understand its potential and limitations

Infrastructure Design Stage Considerations for Environmental Sustainability in Zambia

While previous studies have highlighted the importance of incorporating environmental sustainability in building designs, there is a paucity of studies which assess the extent to which design teams in developing countries consider environmental sustainability at the building design stage. Therefore, using Zambia as a case study, this study examined the extent to which infrastructure design teams in a developing country consider environmental sustainability at the design stage. The study employed a qualitative research approach using structured interviews because there are hardly any studies which have explored the extent to which designers incorporate environmental sustainability in infrastructure designs in developing countries. The data were analysed thematically using the ATLAS.ti software. The results show that environmental sustainability is not an important design consideration because it is secondary to functional, technical and aesthetic considerations. Environmental considerations are also made in an ad-hoc manner and when it is cost effective for the project. Regulatory requirements pertaining to environmental protection are adhered to without any cost considerations. It was therefore theorised that building design teams in developing countries make technical, functional and aesthetic consideration during the infrastructure design stage ahead of environmental considerations. There is a paucity of studies that have investigated whether building infrastructure designers consider issues of environmental sustainability at the design stage in developing countries. The findings have practical implications on how developing countries can foster environmental sustainability at the design stage and avoid generating a building infrastructure stock that will require environmental resilience adaptation in the future

Defeating Paediatric Tuberculous Meningitis: Applying the WHO "Defeating Meningitis by 2030: Global Roadmap"

Children affected by tuberculous meningitis (TBM), as well as their families, have needs that lie at the intersections between the tuberculosis and meningitis clinical, research, and policy spheres. There is therefore a substantial risk that these needs are not fully met by either programme. In this narrative review article, we use the World Health Organization (WHO) “Defeating Meningitis by 2030: global roadmap” as a starting point to consider key goals and activities to specifically defeat TBM in children. We apply the five pillars outlined in the roadmap to describe how this approach can be adapted to serve children affected by TBM. The pillars are (i) prevention; (ii) diagnosis and treatment; (iii) surveillance; (iv) support and care for people affected by meningitis; and (v) advocacy and engagement. We conclude by calling for greater integration between meningitis and TB programmes at WHO and at national levels

Inadequate lopinavir concentrations with modified 8-hourly lopinavir/ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV

BACKGROUND: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment. METHODS: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment. RESULTS: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve 0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; C max 3.04 mg/L [0.03-18.6 mg/L]; C 8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve 24 121.63 mg/h/L [2.56-487.3 mg/h/L]; C max 9.45 mg/L [0.39-26.4 mg/L]; C 12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L. CONCLUSIONS: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation

Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial

BACKGROUND: WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz. METHODS: In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled children from one centre in Zambia and three in Uganda who were previously untreated (ART naive) or on stavudine for more than 2 years with viral load less than 50 copies per mL (ART experienced). Computer-generated randomisation tables were incorporated securely within the database. The primary endpoint was grade 2-4 clinical or grade 3/4 laboratory adverse events. Analysis was intention to treat. This trial is registered with the ISRCTN Registry number, 69078957. FINDINGS: Between Nov 8, 2010, and Dec 28, 2011, 480 children were randomised: 156 to stavudine, 159 to zidovudine, and 165 to abacavir. After two were excluded due to randomisation error, 156 children were analysed in the stavudine group, 158 in the zidovudine group, and 164 in the abacavir group, and followed for median 2·3 years (5% lost to follow-up). 365 (76%) were ART naive (median age 2·6 years vs 6·2 years in ART experienced). 917 grade 2-4 clinical or grade 3/4 laboratory adverse events (835 clinical [634 grade 2]; 40 laboratory) occurred in 104 (67%) children on stavudine, 103 (65%) on zidovudine, and 105 (64%), on abacavir (p=0·63; zidovudine vs stavudine: hazard ratio [HR] 0·99 [95% CI 0·75-1·29]; abacavir vs stavudine: HR 0·88 [0·67-1·15]). At 48 weeks, 98 (85%), 81 (80%) and 95 (81%) ART-naive children in the stavudine, zidovudine, and abacavir groups, respectively, had viral load less than 400 copies per mL (p=0·58); most ART-experienced children maintained suppression (p=1·00). INTERPRETATION: All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines. FUNDING: European Developing Countries Clinical Trials Partnership

Eliciting experts’ tacit models for the interpretation of soil information, an example from the evaluation of potential benefits from conservation agriculture

© 2020 The Authors We examined a procedure to elicit the tacit models underlying expert opinions on environmental factors that affect the absolute yield benefits expected from the adoption of conservation agriculture (CA) practices in southern Africa. The procedure is based on expert evaluation of the expected improvement in crop yield on adoption of CA in a particular scenario or ‘state’, a state being a specified set of soil conditions captured by a standard soil profile description from a specified agroecological zone (AEZ) of Zambia. Mixed groups of scientists including soil scientists, agronomists, agricultural economists and other environmental scientists, facilitated by experienced senior researchers, were presented with multiple subsets each of three states, and asked to rank the states in each subset with respect to expected yield improvement under CA. The groups of scientists could be divided into two sets. Each set comprised two groups, and the agreement on ranking between groups within each set was larger than would be expected if the ranking were done at random. For both sets of groups the ranking could be modelled with respect to properties of the soil, and the contrast between AEZ. The models revealed two contrasting groups of conceptual assumptions. One group broadly expected larger absolute yield improvements from conservation agriculture in settings where water is most likely to be limiting and the carbon status of the soil is poor. By contrast, the other group expected larger improvements where water was less likely to be limiting. These contrasting views are relevant to current discussions as to whether conservation agriculture, which is promoted as a ‘climate smart’ strategy for cropping, is sufficiently attractive for smallholder producers in conditions where crop production is already challenging, and whether the potential benefits in areas where water availability is not of itself a common limitation should be considered. The elicited models could be translated directly into competing hypotheses to be tested, perhaps in on-farm trials of conservation agriculture practices over contrasting soils in the different AEZ. The method, based on modelling the ranking process, could be of more general interest for the elicitation of expert opinion about complex soil, crop and environmental systems

Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and formulations

Background: Dispersible paediatric fixed dose combination (FDCs) tablets delivering higher doses of first-line antituberculosis drugs in WHO-recommended weight-bands were introduced in 2015. We report the first pharmacokinetic data for these FDCs in Zambian and South African children in the treatment-shortening SHINE trial. // Methods: Children weighing 4.0-7.9 kg, 8.0-11.9 kg, 12.0-15.9 kg and 16.0-24.9 kg had 1, 2, 3 and 4 tablets daily (rifampicin/isoniazid/pyrazinamide 75/50/150 mg, with or without 100 mg ethambutol, or rifampicin/isoniazid 75/50 mg), respectively. Children 25.0-36.9 kg received doses recommended for adults <37kg (300, 150, 800, 550 mg daily for rifampicin, isoniazid, pyrazinamide, ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. // Results: Of 77 children evaluated, median (IQR) age was 3.7 (1.4-6.6) years, 40 (52%) were male and 20 (26%) HIV-positive. AUC24 for rifampicin, isoniazid, pyrazinamide and ethambutol were 32.5 (20.1-45.1), 16.7 (9.2 - 25.9), 317 (263 - 399) and 9.5 (7.5 – 11.5) mg.h/L, respectively, and lower in children compared to adults for rifampicin in 4.0-7.9 kg, 8-11.9kg and ≥25kg weight-bands, isoniazid in 4.0-7.9kg and ≥25kg, and ethambutol in all five weight-bands. Pyrazinamide exposures were similar to adults. // Conclusions: Recommended weight-band based FDC doses result in lower drug exposures in children in lower weight-bands and in those ≥25kg (on adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current WHO-recommended doses requires further evaluation

Prevalence and risk factors for Betaherpesvirus DNAemia in children >3 weeks and <2 years of age admitted to a large referral hospital in sub-Saharan Africa

Background. Betaherpesviruses are established causes of morbidity and mortality in immunosuppressed patient groups but have been little studied in sub-Saharan Africa, the epicenter of the human immunodeficiency virus (HIV) pandemic. In this region, primary infections with human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) type 6 are endemic in infancy, but the clinical impact of these infections among pediatric inpatient groups is poorly characterized and assumptive, based largely on data from Western populations. Methods. We used TaqMan polymerase chain reaction to screen sera from a group of 303 pediatric inpatients aged between 3 weeks and 2 years, at the University Teaching Hospital in Lusaka, Zambia. We report the prevalence of DNAemia and viral loads within this patient group, and evaluate possible clinical associations/risk factors for betaherpesvirus infections in these hospitalized children. Results. We detected betaherpesvirus DNAemia in 59.1% (179/303) of children. HCMV was the most prevalent (41.3%), followed by HHV-6B (20.5%), HHV-7 (20.1%), and HHV-6A (0.3%). HIV infection (odds ratio OR], 2.31; 95% confidence interval CI], 1.37-3.90; P = .002), being underweight (OR, 1.82; 95% CI, 1.06-3.12; P = .03), and an admission diagnosis of suspected meningitis (OR, 5.72; 95% CI, 1.07-30.5; P = .041) were independently associated with an increased odds of HCMV DNAemia. Conversely, HHV-6B and HHV-7 DNAemia were not associated with HIV, underweight, or admission diagnosis. Median HCMV viral load was moderately but significantly higher in HIV-infected children. Conclusions. Highly prevalent HCMV DNAemia was independently associated with HIV infection and being underweight across all age groups, and was also associated with meningitis, with previously underappreciated implications for the health and development of African children

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): A study protocol for a randomised controlled trial

BACKGROUND: Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. METHODS/DESIGN: SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. DISCUSSION: Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020