Search

Background: This serological study conducted between March and July 2015 investigated the status of onchocerciasis in Ogun State, Nigeria after a decade of mass drug administration (MDA) with ivermectin. Baseline information from the rapid epidemiological mapping of onchocerciasis (REMO) prior to MDA had indicated that Ogun State was meso-endemic to onchocerciasis. Following years of treatment with ivermectin, it has become important to investigate the current status of the disease using more sensitive diagnostic methods.Methods: The study was conducted in 32 communities in eight onchocerciasis-endemic local government areas (LGAs). Using the Ov16 rapid diagnostic test (Ov16 RDT), finger-prick whole blood was obtained from 3 895 consented participants from age five and above. Skin snips were obtained from a subset of 481 corresponding participants as the majority of community members did not consent to skin snipping.Results: Study revealed a cumulative seroprevalence of 9.3% (CI 9.29–9.31%) by RDT and 17.3% (CI 16.73–18.34%) microfilaridermia prevalence by the skin snip subset. Seroprevalence among children between the ages of five and nine was 2.9% (CI 1.74–3.53%) across all LGAs. A community microfilaria load (CMFL) between 0 and 1.21 MF/skin snip was recorded in the different communities studied. Among the studied LGAs, children in Odeda LGA recorded the highest seroprevalence by RDT (14.9%) followed by Abeokuta North (5.1%), Abeokuta South (4.8%) and Imeko-Afon (0.6%), while Ewekoro, Ifo, Obafemi-Owode and Yewa North LGAs recorded zero prevalence.Conclusion: It appears that the elimination of onchocerciasis in some LGAs is possible considering the lack of new infection among children and the hypo-endemicity among the adult population. However, the microfilaria prevalence observed among adults is of concern as it may imply that mass treatment has not been effective. Increased therapeutic coverage is advised to fully maximise the potential of ivermectin treatment to achieve the disease elimination.

Background Serological assays for human IgG4 to the Onchocerca volvulus antigen Ov16 have been used to confirm elimination of onchocerciasis in much of the Americas and parts of Africa. A standardized source of positive control antibody (human anti-Ov16 IgG4) will ensure the quality of surveillance data using these tests. Methodology/Principal Findings A recombinant human IgG4 antibody to Ov16 was identified by screening against a synthetic human Fab phage display library and converted into human IgG4. This antibody was developed into different positive control formulations for enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT) platforms. Variation in ELISA results and utility as a positive control of the antibody were assessed from multiple laboratories. Temperature and humidity conditions were collected across seven surveillance activities from 2011–2014 to inform stability requirements for RDTs and positive controls. The feasibility of the dried positive control for RDT was evaluated during onchocerciasis surveillance activity in Togo, in 2014. When the anti-Ov16 IgG4 antibody was used as a standard dilution in horseradish peroxidase (HRP) and alkaline phosphatase (AP) ELISAs, the detection limits were approximately 1ng/mL by HRP ELISA and 10ng/mL by AP ELISA. Positive control dilutions and spiked dried blood spots (DBS) produced similar ELISA results. Used as a simple plate normalization control, the positive control antibody may improve ELISA data comparison in the context of inter-laboratory variation. The aggregate temperature and humidity monitor data informed temperature parameters under which the dried positive control was tested and are applicable inputs for testing of diagnostics tools intended for sub-Saharan Africa. As a packaged positive control for Ov16 RDTs, stability of the antibody was demonstrated for over six months at relevant temperatures in the laboratory and for over 15 weeks under field conditions. Conclusions The recombinant human anti-Ov16 IgG4 antibody-based positive control will benefit inter-laboratory validation of ELISA assays and serve as quality control (QC) reagents for Ov16 RDTs at different points of the supply chain from manufacturer to field use., Author Summary Serological markers such as antibody responses to pathogen-specific antigens are used to inform disease epidemiology in many elimination programs. A major challenge with program-scale serological testing, and with any diagnostic test validation, is access to consistent and unlimited control reagents with which to provide assay QC and facilitate data consolidation. In the context of disease elimination, clinical positive sera will be particularly difficult to source and use as routine, inter-laboratory reagents. This study reports on a recombinant antibody specific against a key serological marker for onchocerciasis: its selection, testing, and incorporation into protocols across relevant immunoassay platforms. We have demonstrated it is a viable reagent for integration into QC and QA protocols to support long-term serological testing for onchocerciasis to support disease elimination efforts. This approach should be generalizable to other diagnostic tools supporting programs to achieve the 2020 goals of the London Declaration on Neglected Tropical Diseases.

Background and aim Influenza diagnostics play a critical role informing in clinical management decisions and defining the global epidemiology of the disease to support public health responses. Use of influenza diagnostics within most low‐income and middle‐income countries remains limited, including in the Philippines, where they are currently used only for epidemiologic surveillance. The aim of this study was to define key considerations, including product characteristics, which may influence future adoption, uptake, and integration of influenza diagnostics into public and private clinical settings in this emerging Asian market. Methods Our study was conducted using a convenience sample of public and private hospital laboratories in Metro Manila. A usability assessment was conducted that included interviews with decision‐makers and direct observation of laboratory end users using 2 platforms representative of emerging diagnostic products: (1) a point‐of‐care antigen‐based rapid immunoassay diagnostic test paired with a reader and (2) a molecular diagnostic platform intended for decentralized use. Data were analyzed to assess user errors and device failure modes with each platform and to determine key considerations related to product adoption and uptake. Results The most difficult test step for most users on both platforms involved sample preparation. When deciding to adopt a new test, priority product attributes include performance, potential volume of demand from clinicians, equipment cost, and ease of use. Demand for new tests is likely going to be driven by clinicians, and policies and guidelines will be needed to support the introduction of new products. Conclusion Adoption of influenza diagnostics in Metro Manila is feasible but will require affordable products capable of satisfying needs for use in both epidemiologic surveillance and clinical management.

BACKGROUND: Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. METHODS & FINDINGS: 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3-99.8%), 98.3% (97.5-98.8%), 95.8% (94.0-97.1%), and 99.7% (99.3-99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9-13) days for conventional MODS and 8.5 (7-11) for MODS Kit (p

Introduction Maternal infections continue to be a major contributor to maternal, perinatal, and neonatal morbidity and mortality. The use of diagnostic technologies for maternal infections in the developing world is poorly researched. The current study aimed to elucidate the provider- and patient-level factors that may act to inhibit or encourage timely and effective provision of diagnostic technologies during the pregnancy, intrapartum, and early postpartum periods for infections linked with poor outcomes for mothers and infants in the developing world. Methodology This was an exploratory study that employed a socio-ecological framework. Using qualitative data collection methods, including focus group discussions (FGDs) with pregnant women, new mothers and their families, and in-depth interviews (IDIs) with lower-level providers, we examined health-seeking behaviours and perceptions of diagnostic testing during pregnancy with the aim of obtaining an in-depth understanding of factors related to the potential for uptake of new diagnostic technologies in two developing country settings (Bangladesh and Uganda). Results Diagnostic testing during ANC was generally viewed positively. Findings suggest that women and their families would prefer any proposed diagnostic tests be administered by skilled and trained providers. Communities expressed reservations in providing biological specimens during labour and the immediate postpartum period with discomfort and pain during labour and postpartum confinement cited as reasons for these preferences. Blood and urine were deemed the most acceptable specimens, and vaginal swabs were generally not viewed favourably. While providers were familiar with the concept of diagnostic testing, there is limited use of diagnostics in maternal health care, with HIV testing in Uganda being a notable exception. While providers saw definite advantages of diagnostic testing in terms of patient management, they also expressed reservations about the additional work load this would necessitate. Conclusions There are high levels of receptivity for diagnostic testing among providers and communities with certain caveats regarding specimens and timing.

Background Diagnostics provide a means to measure progress toward disease elimination. Many countries in Africa are approaching elimination of onchocerciasis after successful implementation of mass drug administration programs as well as vector control. An understanding of how markers for infection such as skin snip microfilaria and Onchocerca volvulus-specific seroconversion perform in near-elimination settings informs how to best use these markers. Methods All-age participants from 35 villages in Togo were surveyed in 2013 and 2014 for skin snip Onchocerca volvulus microfilaria and IgG4 antibody response by enzyme-linked immunosorbent assay (ELISA) to the Onchocerca volvulus-specific antigen Ov16. A Gaussian mixture model applying the expectation-maximization (EM) algorithm was used to determine seropositivity from Ov16 ELISA data. For a subset of participants (n = 434), polymerase chain reaction (PCR) was performed on the skin snips taken during surveillance. Results Within the 2,005 participants for which there was Ov16 ELISA data, O. volvulus microfilaremia prevalence and Ov16 seroprevalence were, 2.5 and 19.7 %, respectively, in the total population, and 1.6 and 3.6 % in children under 11. In the subset of 434 specimens for which ELISA, PCR, and microscopy data were generated, it was found that in children under 11 years of age, the anti-Ov16 IgG4 antibody response demonstrate a sensitivity and specificity of 80 and 97 %, respectively, against active infections as determined by combined PCR and microscopy on skin snips. Further analysis was performed in 34 of the 35 villages surveyed. These villages were stratified by all-age seroprevalence into three clusters: < 15 %; 15–20 %; and > 20 %. Age-dependence of seroprevalence for each cluster was best reflected by a two-phase force-of-infection (FOI) catalytic model. In all clusters, the lower of the two phases of FOI was associated with a younger age group, as reflected by the seroconversion rates for each phase. The age at which transition from lower to higher seroconversion, between the two phases of FOI, was found to be highest (older) for the cluster of villages with