Selecting a Laboratory Information System for Biobanks in Low- and Middle-Income Countries

Biobanks in low-and middle-income countries need significant infrastructural support to meet ISBER Best Practices to support population-based genomics research. ISBER recommends a Biobank information management system that can manage workflows from biospecimen receipt to distribution. The H3Africa Initiative was set out to develop regional African Biobanks where Uganda, Nigeria, and South Africa were successfully awarded grants to develop state-of-the-art Biobanks. In this chapter, we review the African experiences, processes, and recommendations for information management systems for use in the low-and middle-income country context. We provide a balanced basis on which institutions can deliberate their decision between an out-of-the-box service and a commercial enterprise

Delays in diagnosis and treatment of pulmonary tuberculosis in patients seeking care at a regional referral hospital, Uganda : a cross sectional study

This study was funded using Authors’ personal resources.Objective: A cross-sectional survey involving 134 pulmonary TB patients started on TB treatment at the TB Treatment Unit of the regional referral hospital was conducted to ascertain the prevalence of individual and health facility delays and associated factors. Prolonged health facility delay was taken as delay of more than 1 week and prolonged patient delay as delay of more than 3 weeks. A logistic regression model was done using STATA version 12 to determine the delays. Results: There was a median total delay of 13 weeks and 110 (82.1%) of the respondents had delay of more than 4 weeks. Patient delay was the most frequent and greatest contributor of total delay and exceeded 3 weeks in 95 (71.6%) respondents. At multivariate analysis, factors that influenced delay included poor patient knowledge on TB (adjOR 6.904, 95% CI 1.648-28.921; p = 0.04) and being unemployed (adjOR 3.947, 95% CI 1.382-11.274; p = 0.010) while being female was found protective of delay; adjOR 0.231, 95% CI 0.08-0.67; p = 0.007). Patient delay was the most significant, frequent and greatest contributor to total delay, and factors associated with delay included being unemployed, low knowledge on TB while being female was found protective of delay.Publisher PDFPeer reviewe

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

Prevalence and Antimicrobial Susceptibility Patterns of Bacteria from Milkmen and Cows with Clinical Mastitis in and around Kampala, Uganda

<div><p>Background</p><p>Identification of pathogens associated with bovine mastitis is helpful in treatment and management decisions. However, such data from sub-Saharan Africa is scarce. Here we describe the distribution and antimicrobial susceptibility patterns of bacteria from cows with clinical mastitis in Kampala, Uganda. Due to high concern of zoonotic infections, isolates from milkmen are also described.</p><p>Methodology/Principal Findings</p><p>Ninety seven milk samples from cows with clinical mastitis and 31 nasal swabs from milkmen were collected (one sample per cow/human). Fifty eight (60%) Gram-positive isolates namely Staphylococci (21), Enterococci (16), Streptococci (13), Lactococci (5), Micrococci (2) and Arcanobacteria (1) were detected in cows; only one grew <i>Staphylococcus aureus</i>. Furthermore, 24 (25%) coliforms namely <i>Escherichia coli</i> (12), <i>Klebsiella oxytoca</i> (5), <i>Proteus vulgaris</i> (2), <i>Serratia</i> (2), <i>Citrobacter</i> (1), <i>Cedecea</i> (1) and <i>Leclercia</i> (1) were identified. From humans, 24 Gram-positive bacteria grew, of which 11 were Staphylococci (35%) including four <i>Staphylococcus aureus</i>. Upon susceptibility testing, methicillin-resistant coagulase-negative staphylococci (CoNS) were prevalent; 57%, 12/21 in cows and 64%, 7/11 in humans. However, methicillin-resistant <i>Staphylococcus aureus</i> was not detected. Furthermore, methicillin and vancomycin resistant CoNS were detected in cows (<i>Staphylococcus hominis</i>, <i>Staphylococcus lugdunensis</i>) and humans (<i>Staphylococcus scuiri</i>). Also, vancomycin and daptomycin resistant Enterococci (<i>Enterococcus faecalis</i> and <i>Enterococcus faecium,</i> respectively) were detected in cows. Coliforms were less resistant with three pan-susceptible isolates. However, multidrug resistant <i>Klebsiella</i>, <i>Proteus</i>, <i>Serratia, Cedecea</i>, and <i>Citrobacter</i> were detected. Lastly, similar species grew from human and bovine samples but on genotyping, the isolates were found to be different. Interestingly, human and bovine <i>Staphylococcus aureus</i> were genetically similar (spa-CC435, spa-type t645 corresponding to ST121) but with different susceptibility patterns.</p><p>Conclusions/Significance</p><p>CoNS, Enterococci, Streptococci, and <i>Escherichia coli</i> are the predominant pathogens associated with clinical bovine-mastitis in Kampala, Uganda. Multidrug resistant bacteria are also prevalent. While similar species occurred in humans and cows, transmission was not detected.</p></div

Prevalence and patterns of rifampicin and isoniazid resistance conferring mutations in <i>Mycobacterium tuberculosis</i> isolates from Uganda

<div><p>Background</p><p>Accurate diagnosis of tuberculosis, especially by using rapid molecular assays, can reduce transmission of drug resistant tuberculosis in communities. However, the frequency of resistance conferring mutations varies with geographic location of <i>Mycobacterium tuberculosis</i>, and this affects the efficiency of rapid molecular assays in detecting resistance. This has created need for characterizing drug resistant isolates from different settings to investigate frequencies of resistance conferring mutations. Here, we describe the prevalence and patterns of rifampicin- and isoniazid- resistance conferring mutations in isolates from Uganda, which could be useful in the management of MDR-TB patients in Uganda and other countries in sub-Saharan Africa.</p><p>Results</p><p>Ninety seven <i>M</i>. <i>tuberculosis</i> isolates were characterized, of which 38 were MDR, seven rifampicin-resistant, 12 isoniazid-mono-resistant, and 40 susceptible to rifampicin and isoniazid. Sequence analysis of the <i>rpoB</i> rifampicin-resistance determining region (<i>rpoB</i>/RRDR) revealed mutations in six codons: 588, 531, 526, 516, 513, and 511, of which Ser531Leu was the most frequent (40%, 18/45). Overall, the three mutations (Ser531Leu, His526Tyr, Asp516Tyr) frequently associated with rifampicin-resistance occurred in 76% of the rifampicin resistant isolates while 18% (8/45) of the rifampicin-resistant isolates lacked mutations in <i>rpoB</i>/RRDR. Furthermore, sequence analysis of <i>katG</i> and <i>inhA</i> gene promoter revealed mainly the Ser315Thr (76%, 38/50) and C(-15)T (8%, 4/50) mutations, respectively. These two mutations combined, which are frequently associated with isoniazid-resistance, occurred in 88% of the isoniazid resistant isolates. However, 20% (10/50) of the isoniazid-resistant isolates lacked mutations both in <i>katG</i> and <i>inhA</i> gene promoter. The sensitivity of sequence analysis of <i>rpoB</i>/RRDR for rifampicin-resistance via detection of high confidence mutations (Ser531Leu, His526Tyr, Asp516Tyr) was 81%, while it was 77% for analysis of <i>katG</i> and <i>inhA</i> gene promoter to detect isoniazid-resistance via detection of high confidence mutations (Ser315Thr, C(-15)T, T(-8)C). Furthermore, considering the circulating TB genotypes in Uganda, the isoniazid-resistance conferring mutations were more frequent in <i>M</i>. <i>tuberculosis</i> lineage 4/sub-lineage Uganda, perhaps explaining why this genotype is weakly associated with MDR-TB.</p><p>Conclusion</p><p>Sequence analysis of <i>rpoB</i>/RRDR, <i>katG</i> and <i>inhA</i> gene promoter is useful in detecting rifampicin/isoniazid resistant <i>M</i>. <i>tuberculosis</i> isolates in Uganda however, about ≤20% of the resistant isolates lack known resistance-conferring mutations hence rapid molecular assays may not detect them as resistant.</p></div

Distinct patterns among staphylococci (panel A), enterococci (panel B) and streptococci (panel C) following RAPD genotyping.

<p>One isolate per lane.</p

Antimicrobial resistance patterns among coliforms (n = 24).

<p>AMP, Ampicillin; AMO; Amoxicillin-Clavulanate; SXT, trimethopprim-sulfamethoxazole; COL, Colistin; IMP, imipenem; CEF, Cefoxitine; CFT, Cefotaxim; CEP, Cephalothin; CFU, Cefuroxime; CFP, Cefepime; AZT, Aztreonam; ERY, Erythromycin; NTR, Nitrofurantoin; PIP, Piperacillin-Tazobactum; ERT, Ertapenem.</p><p>In boldface type are isolates found to be multi-drug resistant (MDR).</p

Antimicrobial resistance among staphylococci from cows (panel A) and milkmen (panel B).

<p>Details in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063413#pone.0063413.s001" target="_blank">Tables S1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063413#pone.0063413.s002" target="_blank">S2</a>.</p