Mannitol in diuretic resistant nephrotic syndrome: a case report

A 6 year old presented with generalized oedema to Kagando hospital, Uganda, and was diagnosed with nephrotic syndrome. Despite treatment with a fluid restriction, prednisolone and furosemide, the oedema worsened and the weight increased. Mannitol was added to the treatment regime and the oedema improved. The patient was able to be discharged four days later without any diuretic therapy. The case highlights the use of mannitol in the treatment of diuretic resistant oedema with nephrotic syndrome. It provides an alternative therapy for the resource-poor setting to the expensive albumin-furosemide combination often used elsewhere

Molecular characterisation of echinococcus granulosus species/strains in human infections from Turkana, Kenya

Background: Cystic echinococcosis (CE) or hydatid disease is a neglected, economically important zoonotic disease endemic in pastoralist communities, in particular the Turkana community of Kenya. It is caused by the larval stage of the highly diverse species complex of Echinococcus granulosus sensu lato (s.l). The situation on the genetic diversity in humans in Kenya is not well established.Objective: To characterise Echinococcus granulosus (s.l) species/strains isolated from humans undergoing surgery in Turkana, Kenya.Design: A Cross sectional study.Setting: The Kakuma Mission Hospital and Centre for Microbiology Research, Kenya Medical Research InstituteSubjects: Eighty (80) parasite samples from 26 subjects were analysed by Polymerase chain reaction – Restriction fragment length polymorphism (PCR-RFLP) targeting the nad 1 gene for molecular characterizationResults: Two different genotypes of E. granulosus were identified from the samples analysed: E. granulosus sensu stricto (G1-G3) 85% of the samples analysed and E. canadensis G6/7 (15%). Most of the hydatid cysts (35%) were isolated from the liver. Other sites where cysts were isolated from include: kidney, abdomen, omentum, retroperitonium and the submandibular. Majority of cysts presented as CE1 (50%) and CE3B (42%) images according to WHO ultrasound classification. Both males and females were infected with E. granulosus s.s but only the females showed infection with E. canadensis G6/7. Chi-square test revealed significant difference between age of individuals and cysts classification by ultrasound. In addition, there was an association between cyst presentation (single or multiple) and genotype whereby all the E. canadensis G6/7 cases presented as single cysts in the infected persons.Conclusion: This study corroborates previous reports that E. canadensis G6/7 strain is present in Turkana, a place where initially only E. granulosus s.s (G1-G3) was known to be present and that E. granulosis (G1-G3) remains the most widespread genotype infecting humans in the Turkana community

Infection and Vertical Transmission of Kamiti River Virus in Laboratory Bred Aedes aegypti Mosquitoes

Kamiti river virus (KRV) is an insect-only Flavivirus that was isolated from field-collected Ae. macintoshi mosquitoes in 1999, and is closely related to cell fusing agent virus. Both of these viruses belong to the family Flaviviridae, which also contains other viruses of medical importance, such as yellow fever virus, West Nile virus and dengue. Because Ae. macintoshi is the only known natural host to KRV, the main objective of this study was to establish the possibility that other mosquito hosts of the virus exist, by determining its ability to infect Ae. aegypti mosquitoes under laboratory conditions. The study also sought to determine the rates of infection and, subsequently, vertical transmission as a possible means of its maintenance and propagation in nature, given that it neither grows in vertebrate cells or mice. The mosquitoes were infected by the virus either as larvae or adults. Virus assay was done by re-isolation in tissue culture and indirect immunofluoresce assay methods. KRV infected Ae. aegypti mosquitoes, with the observed rates as high as 74 to 96 %. The virus was also transmitted vertically in these mosquitoes. Vertical transmission rates of 3.90 % were observed for the 2nd and 3rd ovarian cycles combined. These results suggest that Ae. aegypti mosquitoes are likely to be infected with KRV in nature, and that vertical transmission is the natural means by which it is maintained and propagated in this host, and possibly others

In vitro embryo rescue and plant regeneration following self-pollination with irradiated pollen in cassava (Manihot esculenta Crantz)

Cassava is a highly heterozygous species; hence, current methods used in classical cassava breedingcannot match the urgent need to high yielding varieties. Recently, progress was made through androgenesis and gynogenesis as pathways for raising doubled cassava haploid lines to overcome problems associated with cassava’s inherent reproductive biology, but these efforts were limited (nocandidate cassava plantlets were regenerated). For the first time, this study shows that pollen irradiation coupled with self-pollination and embryo rescue regenerated 62 candidate cassava plantlets. Plants of an elite cassava variety, Nase14, served as a mother plant and as the pollen donor for the irradiation. Irradiation dosages of 50 to 250 Gray studied across five pollination events and 300 or 500 Gray in one pollination event caused a reduction in pollen germination up to 67.0%. By 15 days after pollination (DAP) with irradiated pollen, up to 89.7% of the pollinated flowers had aborted. By embryo rescue time (42 DAP), significant differences were observed in number of fruits, seeds and embryos generated, with the non-irradiated pollen treatments having significantly higher numbers. Sixteen (16) heterozygous SSR markers in the parent and ploidy analysis showed that none of the regenerated plants was haploid or homozygous. However, the plantlets resulting from pollination with non-irradiated pollen had 56.2% homozygous loci, while progeny derived from irradiated treatments had frequencies of homozygous loci between 28.1 and 55.0%. This is the first time to use irradiated pollen in cassava as a pathway to generate candidate plantlets as an initial step in double haploid production.Key words: Cassava, doubled haploids, embryo rescue, plant regeneration, pollen germination, pollenirradiation

Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda

Background: Individuals genetically susceptible to high schistosomiasis worm burden may contribute disproportionately to transmission and could be prioritized for control. Identifying genes involved may guide development of therapy. // Methodology/Principal findings: A cohort of 606 children aged 10–15 years were recruited in the Albert Nile region of Uganda and assessed for Schistosoma mansoni worm burden using the Up-Converting Particle Lateral Flow (UCP-LF) test detecting circulating anodic antigen (CAA), point-of-care Circulating Cathodic Antigen (POC-CCA) and Kato-Katz tests. Whole genome genotyping was conducted on 326 children comprising the top and bottom 25% of worm burden. Linear models were fitted to identify variants associated with worm burden in preselected candidate genes. Expression quantitative trait locus (eQTL) analysis was conducted for candidate genes with UCP-LF worm burden included as a covariate. Single Nucleotide Polymorphism loci associated with UCP-LF CAA included IL6 rs2066992 (OR = 0.43, p = 0.0006) and rs7793163 (OR = 2.0, p = 0.0007); IL21 SNP kgp513476 (OR 1.79, p = 0.0025) and IL17B SNP kgp708159 (OR = 0.35, p = 0.0028). A haplotype in the IL10 locus was associated with lower worm burden (OR = 0.53, p = 0.015) and overlapped SNPs rs1800896, rs1800871 and rs1800872. Significant haplotypes (p<0.05, overlapping significant SNP) associated with worm burden were observed in IL6 and the Th17 pathway IL12B and IL17B genes. There were significant eQTL in the IL6, IL5, IL21, IL25 and IFNG regions. // Conclusions: Variants associated with S. mansoni worm burden were in IL6, FCN2, RNASE3, IL10, IL12B and IL17B gene loci. However only eQTL associations remained significant after Bonferroni correction. In summary, immune balance, pathogen recognition and Th17 pathways may play a role in modulating Schistosoma worm burden. Individuals carrying risk variants may be targeted first in allocation of control efforts to reduce the burden of schistosomiasis in the community

Integrated Mapping of Neglected Tropical Diseases: Epidemiological Findings and Control Implications for Northern Bahr-el-Ghazal State, Southern Sudan

Integrated control of neglected tropical diseases (NTDs) is being scaled up in a number of developing countries, because it is thought to be more cost-effective than stand-alone control programmes. Under this approach, treatments for onchocerciasis, lymphatic filariasis (LF), schistosomiasis, soil-transmitted helminth (STH) infection, and trachoma are administered through the same delivery structure and at about the same time. A pre-requisite for implementation of integrated NTD control is information on where the targeted diseases are endemic and to what extent they overlap. This information is generated through surveys that can be labour-intensive and expensive. In Southern Sudan, all of the above diseases except onchocerciasis require further mapping before a comprehensive integrated NTD control programme can be implemented. To determine where treatment for which disease is required, integrated surveys were conducted for schistosomiasis, STH infection, LF, and loiasis, throughout one of ten states of the country. Our results show that treatment is only required for urinary schistosomiasis and STH in a few, yet separate, geographical area. This illustrates the importance of investing in disease mapping to minimize overall programme costs by being able to target interventions. Integration of survey methodologies for the above disease was practical and efficient, and minimized the effort required to collect these data

Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda

Objectives We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring. Methods NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm3) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL. Phenotypic resistance was expressed as fold-change in IC50 (FC) relative to wild-type virus. Results HIV-1 RNA viral load ≥1000 copies/mL at week 96 was seen in 58/204 (28.4%) cABC participants and 21/159 (13.2%) cNVP participants. Resistance results were available in 35 cABC and 17 cNVP participants; 31 (89%) cABC and 16 (94%) cNVP isolates had a week 96 FC below the biological cut-off for tenofovir (2.2). In the cNVP arm, 16/17 participants had resistance mutations synonymous with high-level resistance to nevirapine and efavirenz; FC values for etravirine were above the biological cut-off in 9 (53%) isolates. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm. Conclusions Our data support the use of tenofovir following failure of a first-line zidovudine-containing regimen and shed further light on non-nucleoside reverse transcriptase inhibitor hypersusceptibility

No evidence for association with APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations:

Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken a candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT