Ross Boyce

Bacillus thuringiensis israelensis (Bti) for the control of dengue vectors: systematic literature review.

To systematically review the literature on the effectiveness of Bacillus thuringiensis israelensis (Bti), when used as a single agent in the field, for the control of dengue vectors.

Dengue data and surveillance in Tanzania: a systematic literature review

Although there is evidence that dengue virus is circulating in Tanzania, the country lacks a dengue surveillance system. Consequently, the true estimate of dengue seroprevalence, as well as the incidence in the population, the frequency and magnitude of outbreaks is unknown. This study therefore sought to systematically review available dengue data from Tanzania.

Practical Implications of the Non-Linear Relationship between the Test Positivity Rate and Malaria Incidence

Background The test positivity rate (TPR), defined as the number of laboratory-confirmed malaria tests per 100 suspected cases examined, is widely used by malaria surveillance programs as one of several key indicators of temporal trends in malaria incidence. However, there have been few studies using empiric data to examine the quantitative nature of this relationship. Methods To characterize the relationship between the test positivity rate and the incidence of malaria, we fit regression models using the confirmed malaria case rate as the outcome of interest and TPR as the predictor of interest. We varied the relationship between the two by alternating linear and polynomial terms for TPR, and compared the goodness of fit of each model. Results A total of 7,668 encounters for malaria diagnostic testing were recorded over the study period within a catchment area of 25,617 persons. The semi-annual TPR ranged from 4.5% to 59% and the case rates ranged from 0.5 to 560 per 1,000 persons. The best fitting model was an exponential growth model (R2 = 0.80, AIC = 637). At low transmission levels (TPR<10%), the correlation between TPR and CMCR was poor, with large reductions in the TPR, for example from 10% to 1%, was associated with a minimal change in the CMCR (3.9 to 1.7 cases per 1,000 persons). At higher transmission levels, the exponential relationship made relatively small changes in TPR suggestive of sizeable change in estimated malaria incidence, suggesting that TPR remains a valuable surveillance indicator in such settings. Conclusions The TPR and the confirmed malaria case rate have a non-linear relationship, which is likely to have important implications for malaria surveillance programs, especially at the extremes of transmission.

Association between HRP-2/pLDH rapid diagnostic test band positivity and malaria-related anemia at a peripheral health facility in Western Uganda.

The detection of severe malaria in resource–constrained settings is often difficult because of requirements for laboratory infrastructure and/or clinical expertise. The aim of this study, therefore, was to explore the utility of a multiple antigen (HRP–2/pLDH) rapid diagnostic test (RDT) as a low–cost, surrogate marker of patients at high risk for complications of severe malaria. We reviewed programmatic data at a peripheral health center in Western Uganda. Available demographic and clinical data on all individuals presenting to the center who underwent an RDT for suspected malaria infection were reviewed. We fit logistic regression models to identify correlates of two outcomes of interest: 1) severe malaria–related anemia, defined here as hemoglobin ≤7g/dL and 2) receipt of parenteral quinine. 1509 patients underwent malaria testing with an SD FK60 RDT during the observation period. A total of 637 (42%) RDTs were positive for at least one species of malaria, of which 326 (51%) exhibited a single HRP–2 band and 307 (48%) exhibited both HRP–2 and pLDH bands, while 4 exhibited only a single pLDH band. There was a trend towards more severe anemia in patients with a HRP–2/pLDH positive RDT compared to a HRP–2 only RDT (β = –0.99 g/dl, 95% CI –1.99 to 0.02, P = 0.055). A HRP–2/pLDH positive RDT was associated with an increased risk of severe malaria–related anemia compared to a negative RDT (adjusted odds ratio (AOR) 18.8, 95% CI 4.32 to 82.0, P < 0.001) and to a HRP–2 only RDT (AOR 2.46, 95% CI 0.75 to 8.04, P = 0.14). There was no significant association between RDT result and the administration of parenteral quinine. These results offer preliminary evidence that specific patterns of antigen positivity on RDTs could be utilized to identify patients at an increased risk for complications of severe malaria.

Community effectiveness of pyriproxyfen as a dengue vector control method: A systematic review

Background Vector control is the only widely utilised method for primary prevention and control of dengue. The use of pyriproxyfen may be promising, and autodissemination approach may reach hard to reach breeding places. It offers a unique mode of action (juvenile hormone mimic) and as an additional tool for the management of insecticide resistance among Aedes vectors. However, evidence of efficacy and community effectiveness (CE) remains limited. Objective The aim of this systematic review is to compile and analyse the existing literature for evidence on the CE of pyriproxyfen as a vector control method for reducing Ae. aegypti and Ae. albopictus populations and thereby human dengue transmission. Methods Systematic search of PubMed, Embase, Lilacs, Cochrane library, WHOLIS, Web of Science, Google Scholar as well as reference lists of all identified studies. Removal of duplicates, screening of abstracts and assessment for eligibility of the remaining studies followed. Relevant data were extracted, and a quality assessment conducted. Results were classified into four main categories of how pyriproxyfen was applied: - 1) container treatment, 2) fumigation, 3) auto-dissemination or 4) combination treatments,–and analysed with a view to their public health implication. Results Out of 745 studies 17 studies were identified that fulfilled all eligibility criteria. The results show that pyriproxyfen can be effective in reducing the numbers of Aedes spp. immatures with different methods of application when targeting their main breeding sites. However, the combination of pyriproxyfen with a second product increases efficacy and/or persistence of the intervention and may also slow down the development of insecticide resistance. Open questions concern concentration and frequency of application in the various treatments. Area-wide ultra-low volume treatment with pyriproxyfen currently lacks evidence and cannot be recommended. Community participation and acceptance has not consistently been successful and needs to be further assessed. While all studies measured entomological endpoints, only two studies measured the reduction in human dengue cases, with inconclusive results. Conclusions Although pyriproxyfen is highly effective in controlling the immature stages of dengue transmitting mosquitoes, and–to a smaller degree–adult mosquitoes, there is weak evidence for a reduction of human dengue cases. More well designed larger studies with appropriate standardised outcome measures are needed before pyriproxyfen is incorporated in routine vector control programmes. Additionally, resistance to pyriproxyfen has been reported and needs investigation.

Community effectiveness of indoor spraying as a dengue vector control method: A systematic review

Background The prevention and control of dengue rely mainly on vector control methods, including indoor residual spraying (IRS) and indoor space spraying (ISS). This study aimed to systematically review the available evidence on community effectiveness of indoor spraying. Methods A systematic review was conducted using seven databases (PubMed, EMBASE, LILACS, Web of Science, WHOLIS, Cochrane, and Google Scholar) and a manual search of the reference lists of the identified studies. Data from included studies were extracted, analysed and reported. Results The review generated seven studies only, three IRS and four ISS (two/three controlled studies respectively). Two IRS studies measuring human transmission showed a decline. One IRS and all four ISS studies measuring adult mosquitoes showed a very good effect, up to 100%, but not sustained. Two IRS studies and one ISS measuring immature mosquitoes, showed mixed results. Conclusions It is evident that IRS and also ISS are effective adulticidal interventions against Aedes mosquitoes. However, evidence to suggest effectiveness of IRS as a larvicidal intervention and to reduce human dengue cases is limited–and even more so for ISS. Overall, there is a paucity of studies available on these two interventions that may be promising for dengue vector control, particularly for IRS with its residual effect.

Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm

ABSTRACT Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan-lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2+)/pLDH-negative (pLDH−) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2+/pLDH+ result, 94 (34.1%) with an HRP2+/pLDH− result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2+/pLDH− results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2+/pLDH− results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting.

The Health Centre Community

The greatest burden of malaria is borne by the children of rural sub-Saharan Africa. Each year nearly 90% of all malaria-related deaths occur in these remote areas, far from lifesaving medical care. In the Bugoye sub-county of rural Western Uganda, most families subsist on small plots of staple crops carved into the hillsides. Lacking transportation, worried parents carry their sick children down the narrow mountain paths to the health centre in search of care (Figure 1). The Level III Health Centre in Bugoye is the only facility in the sub-county—an area spanning more than 40 villages and nearly 60 km—equipped to treat cases of severe malaria. During the high season, hundreds of malaria-stricken children come to the health centre each week for diagnosis and treatment (Figure 2). Like many public health facilities in rural sub-Saharan Africa, the Bugoye Health Centre faces many challenges, including drug shortages, unreliable electrical power and inadequate staffing. The health centre is not shiny or new. There are no private rooms. The unfinished cement floors are cracked, the paint is peeling, the thin foam mattresses are worn and tattered and most of the equipment is decades old (Figure 3). What Bugoye does have, however, is a vibrant sense of community. In many ways, the health centre has the atmosphere of a bustling village unto itself. It is the heart of the sub-county. Entire families inhabit the wards, providing food, linen and clothing for their sick loved ones (Figures 4 and 5).The bright colours of children in church clothes dot the yard and groups of women gather behind the clinic, preparing meals over open fires (Figure 6). Village officials, health centre staff and local tradesmen sit on the benches at the front to wave to friends, chat about

Use of a bibliometric literature review to assess medical research capacity in post‐conflict and developing countries: Somaliland 1991–2013

Effective healthcare systems require high‐quality research to guide evidence‐based interventions and strategic planning. In low‐ and middle‐income countries, especially those emerging from violent conflict, research capacity often lags behind other aspects of health system development. Here, we sought to bibliometrically review health‐related research output in Somaliland, a post‐conflict self‐declared, autonomous nation on the Horn of Africa, as a means of assessing research capacity.

Waiver of Consent: The Use of Pyridostigmine Bromide during the Persian Gulf War

Abstract In 1990, issues of individual autonomy and informed consent came to the forefront when the United States Department of Defense requested and eventually obtained a waiver from the Food and Drug Administration authorizing the use of investigational compounds in soldiers without their informed consent. This article reviews the concepts of autonomy and informed consent within the military, and examines the history and ethical debate surrounding the Interim Rule. The author suggests that an ethical impasse will continue to exist so long it remains morally unacceptable to expose human subjects to chemical agents for the purposes of research. Yet definitional constraints should not preclude the development of potentially beneficial compounds in appropriate circumstances. The author proposes criteria to establish an investigational agent as standard of care. Using this set of criteria, he examines the use of pyridostigmine bromide during the 1991 Persian Gulf War, a notable decision given the strong association between the agent and Gulf War Illness. A detailed review concludes that the agent in question cannot be considered standard-of-care treatment and that the compulsory administration of the compound without informed consent constituted a violation of the principle outlined in the landmark bioethics documents of the twentieth century.