Trop. Med. Infect. Dis., Volume 5, Issue 1 (March 2020) – 47 articles

Canine rabies elimination can be achieved through mass vaccination of the dog population, as advocated by the WHO, OIE and FAO under the ‘United Against Rabies’ initiative. Many countries in which canine rabies is endemic are exploring methods to access dogs for vaccination, campaign structures and approaches to resource mobilization. Reviewing aspects that fostered success in rabies elimination campaigns elsewhere, as well as examples of largescale resource mobilization, such as that seen in the global initiative to eliminate poliomyelitis, may help to guide the planning of sustainable, scalable methods for mass dog vaccination. Elimination of rabies from the majority of Latin America took over 30 years, with years of operational trial and error before a particular approach gained the broad support of decision makers, governments and funders to enable widespread implementation. The endeavour to eliminate polio now enters its final stages; however, there are many transferrable lessons to adopt from the past 32 years of global scale-up. Additionally, there is a need to support operational research, which explores the practicalities of mass dog vaccination roll-out and what are likely to be feasible solutions at scale. This article reviews the processes that supported the scale-up of these interventions, discusses pragmatic considerations of campaign duration and work-force size and finally provides an examples hypothetical resource requirements for implementing mass dog vaccination at scale in Indian cities, with a view to supporting the planning of pilot campaigns from which expanded efforts can grow. Full article

Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that has been extensively characterized in human disease and in mouse models. Its pro-inflammatory functions in mammals includes the retention of tissue macrophages and a unique ability to counteract the immunosuppressive activity of glucocorticoids. MIF also acts as a survival factor by preventing activation-induced apoptosis and by promoting sustained expression of inflammatory factors such as TNF-α and nitric oxide. The pro-inflammatory activity of MIF has been shown to be protective against Leishmania major infection in mouse models of cutaneous disease, however the precise role of this cytokine in human infections is less clear. Moreover, various species of Leishmania produce their own MIF orthologs, and there is evidence that these may drive an inflammatory environment that is detrimental to the host response. Herein the immune response to Leishmania in mouse models and humans will be reviewed, and the properties and activities of mammalian and Leishmania MIF will be integrated into the current understandings in this field. Furthermore, the prospect of targeting Leishmania MIF for therapeutic purposes will be discussed. Full article

To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061–0.069; n = 346), and that 88% (95% CI 80.7–93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83–2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24–7.69) and the HR in males 0.79 (95% CI 0.41–1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11–0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms. Full article

An elderly Singaporean male with no travel history was hospitalized for fever and altered mental status. Blood cultures grew Enterococcus faecalis, and given a preceding history of steroid use and peripheral eosinophilia, Strongyloides hyperinfection was suspected. Stool specimens were positive for Strongyloides stercoralis larvae over four days, and larvae were also isolated in an early morning nasogastric aspirate specimen prior to initiation of ivermectin. A cerebrospinal fluid examination was consistent with partially treated bacterial meningitis and ventriculitis was demonstrated on neuroimaging. In view of a persistent fever, a further imaging evaluation was performed, which demonstrated bilateral pneumonia as well as the unusual finding of gas-forming emphysematous spondylodiscitis and left psoas abscesses. Despite the early suspicion of Strongyloides hyperinfection, commencement of appropriate antibiotics and anti-helminthics, microbiological clearance of bacteremia as well as clearance of S. stercoralis from the stool, the patient still succumbed to infection and passed away 11 days after admission. Full article

Vietnam has been using a levofloxacin-based shorter treatment regimen (STR) for rifampicin resistant/multidrug-resistant tuberculosis (RR/MDR-TB) patients since 2016 on a pilot basis. This regimen lasts for 9–11 months and is provided to RR/MDR-TB patients without second-line drug resistance. We report the treatment outcomes and factors associated with unsuccessful outcomes. We conducted a cohort study involving secondary analysis of data extracted from electronic patient records maintained by the national TB program (NTP). Of the 302 patients enrolled from April 2016 to June 2018, 259 (85.8%) patients were successfully treated (246 cured and 13 ‘treatment completed’). Unsuccessful outcomes included: treatment failure (16, 5.3%), loss to follow-up (14, 4.6%) and death (13, 4.3%). HIV-positive TB patients, those aged ≥65 years and patients culture-positive at baseline had a higher risk of unsuccessful outcomes. In a sub-group of patients enrolled in 2016 (n = 99) and assessed at 12 months after treatment completion, no cases of relapse were identified. These findings vindicate the decision of the Vietnam NTP to use a levofloxacin-based STR in RR/MDR-TB patients without second-line drug resistance. This regimen may be considered for nationwide scale-up after a detailed assessment of adverse drug events. Full article

In the early 20th century, a series of epidemics across equatorial Africa brought African sleeping sickness (human African trypanosomiasis, HAT) to the attention of the European colonial administrations. This disease presented an exciting challenge for microbiologists across Europe to study the disease, discover the pathogen and search for an effective treatment. In 1923, the first “remedy for tropical diseases”—Suramin—manufactured by Bayer AG came onto the market under the brand name “Germanin.” The development and life cycle of this product—which today is still the medicine of choice for Trypanosoma brucei (T.b), hodesiense infections—reflect medical progress as well as the successes and failures in fighting the disease in the context of historic political changes over the last 100 years. Full article

Antiretroviral therapy (ART) coverage among HIV-infected tuberculosis (HIV-TB) patients has been suboptimal in Myanmar and the reasons are unknown. We aimed to assess the ART uptake among HIV-TB patients in public health facilities of Ayeyawady Region from July 2017–June 2018 and explore the barriers for non-initiation of ART. We conducted an explanatory mixed-methods study with a quantitative component (cohort analysis of secondary programme data) followed by a descriptive qualitative component (thematic analysis of in-depth interviews of 22 providers and five patients). Among 12,447 TB patients, 11,057 (89%) were HIV-tested and 627 (5.7%) were HIV-positive. Of 627 HIV-TB patients, 446 (71%) received ART during TB treatment (86 started on ART prior to TB treatment and rest started after TB treatment). Among the 181 patients not started on ART, 60 (33%) died and 41 (23%) were lost-to-follow-up. Patient-related barriers included geographic and economic constraints, poor awareness, denial of HIV status, and fear of adverse drug effects. The health system barriers included limited human resource, provision of ART on ‘fixed’ days only, weaknesses in counselling, referral and feedback mechanism, and clinicians’ reluctance to start ART early due to concerns about immune reconstitution inflammatory syndrome. We urge the national TB and HIV programs to take immediate actions to improve the ART uptake. Full article

The purified Vero cell rabies vaccine (PVRV; Verorab^®, Sanofi Pasteur) has been used in rabies prevention since 1985. Evolving rabies vaccination trends, including shorter intradermal (ID) regimens with reduced volume, along with WHO recommendation for ID administration has driven recent ID PVRV regimen assessments. Thus, a consolidated review comparing immunogenicity of PVRV ID regimens during pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is timely and beneficial in identifying gaps in current research. A search of seven databases for studies published from 1985 to November 2019 identified 35 studies. PrEP was assessed in 10 studies (n = 926) with 1–3-site, 1–3-visit regimens of up to 3-months duration. Seroconversion (rabies virus neutralizing antibodies [RVNA] ≥ 0.5 IU/mL) rates of 90–100% were reported within weeks, irrespective of regimen, with robust booster responses at 1 year (100% seroconversion rates by day 14 post-booster). However, data are lacking for the current WHO-recommended, 2-site, 1-week ID PrEP regimen. PEP was assessed in 25 studies (n = 2136) across regimens of 1-week to 90-day duration. All ID PEP regimens assessed induced ≥ 99% seroconversion rates (except in HIV participants) by day 14–28. This review confirms ID PVRV suitability for rabies prophylaxis and highlights the heterogeneity of use in the field. Full article

Gnathostomiasis is a zoonotic nematode parasite disease, most commonly acquired by eating raw or undercooked fish. Although the disease is well known in parts of Asia and Central and South America, relatively few cases have been reported from Africa. Raw fish consumed in the Okavango River delta area of Botswana, and in nearby western Zambia, has previously produced laboratory-proven gnathostomiasis in tourists. The purpose of this communication is to record additional cases of the infection acquired in the Okavango delta, and to alert visitors to the inadvisability of eating raw freshwater fish in the southern African region. Full article

Zika virus (ZIKV) circulates as two separate lineages, with significant genetic variability between strains. Strain-dependent activity has been reported for dengue virus, herpes simplex virus and influenza. Strain-dependent activity of subject specimens to a virus could be an impediment to serological diagnosis and vaccine development. In order to determine whether ZIKV exhibits strain-dependent activity when exposed to antibodies, we measured the neutralizing properties of polyclonal serum and three monoclonal antibodies (ZKA185, 753(3)C10, and 4G2) against three strains of ZIKV (MR−766, PRVABC59, and R103454). Here, MR−766 was inhibited almost 60% less by ZKA185 than PRVABC59 and R103454 (p = 0.008). ZKA185 enhanced dengue 4 infection up to 50% (p = 0.0058). PRVABC59 was not inhibited by mAb 753(3)C10 while MR−766 and R103453 were inhibited up to 90% (p = 0.04 and 0.036, respectively). Patient serum, regardless of exposure history, neutralized MR−766 ~30%−40% better than PRVABC56 or R103454 (p = 0.005−0.00007). The most troubling finding was the significant neutralization of MR−766 by patients with no ZIKV exposure. We also evaluated ZIKV antibody cross reactivity with various flaviviruses and found that more patients developed cross-reactive antibodies to Japanese encephalitis virus than the dengue viruses. The data here show that serological diagnosis of ZIKV is complicated and that qualitative neutralization assays cannot discriminate between flaviviruses. Full article

Flea-borne typhus, due to Rickettsia typhi and Rickettsia felis, is an infection causing fever, headache, rash, hepatitis, thrombocytopenia, and diverse organ manifestations. Although most cases are self-limited, 26%–28% have complications and up to one-third require intensive care. Flea-borne typhus was recognized as an illness similar to epidemic typhus, but having a milder course, in the Southeastern United States and TX from 1913 into the 1920s. Kenneth Maxcy of the US Public Health Service (USPHS) first described the illness in detail and proposed a rodent reservoir and an arthropod vector. Other investigators of the USPHS (Eugene Dyer, Adolph Rumreich, Lucius Badger, Elmer Ceder, William Workman, and George Brigham) determined that the brown and black rats were reservoirs and various species of fleas, especially the Oriental rat flea, were the vectors. The disease was recognized as a health concern in the Southern United States in the 1920s and an increasing number of cases were observed in the 1930s and 1940s, with about 42,000 cases reported between 1931–1946. Attempts to control the disease in the 1930s by fumigation and rat proofing and extermination were unsuccessful. The dramatic increase in the number of cases from 1930 through 1944 was due to: the diversification of Southern agriculture away from cotton; the displacement of the smaller black rat by the larger brown rat in many areas; poor housing conditions during the Great Depression and World War II; and shortages of effective rodenticides and insecticides during World War II. Full article

People’s knowledge, attitudes, practices and beliefs (KAPB) pertaining to malaria are generally well described. However, little is known about population knowledge and awareness of insecticide resistance in malaria vectors. The aim of this study was to investigate KAPB related to insecticide resistance in malaria vectors due to the use of insecticides in agriculture and the prevention against mosquitoes. In mid-2017, we carried out a cross-sectional survey in Elibou, South Côte d’Ivoire, employing a mixed methods approach. Quantitative data were obtained with a questionnaire addressed to household heads. Interviews were conducted with key opinion leaders, including village chiefs, traditional healers, heads of health centres and pesticide sellers. Focus group discussions were conducted with youth and elders. A total of 203 individuals participated in the questionnaire survey (132 males, 65%). We found that people had good knowledge about malaria and mosquitoes transmitting the disease, while they felt that preventing measures were ineffective. Pesticides were intensively used by farmers, mainly during the rainy season. Among the pesticides used, insecticides and herbicides were most commonly used. While there was poor knowledge about resistance, the interviewees stated that insecticides were not killing the mosquitoes anymore. The main reason given was that insecticides were diluted by the manufacturers as a marketing strategy to sell larger quantities. More than a third of the farmers used agricultural pesticides for domestic purposes to kill weeds or mosquitoes. We observed a misuse of pesticides among farmers, explained by the lack of specific training. In the community, long-lasting insecticidal nets were the most common preventive measure against malaria, followed by mosquito coils and insecticide sprays. The interviewees felt that the most effective way of dealing with insecticide resistance was to combine at least two preventive measures. In conclusion, population attitudes and practices related to insecticides used in agriculture and the prevention against mosquitoes could lead to resistance in malaria vectors, while people’s knowledge about insecticide resistance was limited. There is a need to raise awareness in communities about the presence of resistance in malaria vectors and to involve them in resistance management. Full article

Rabies surveillance and control measures vary significantly between Caribbean islands. The Centers for Disease Control and Prevention currently recommends certain groups of U.S. travelers to any Caribbean island receive pre-exposure rabies immunization. However, most islands self-declare as “rabies free”, and have never publicly released data to support rabies-free claims. We used the Analytic Hierarchy Process to create pairwise comparison values among five risk factors determined by subject matter experts. Risk factor weights were calculated and used in a geospatial analysis to calculate a risk value for each island nation (higher values indicate higher risk). Risk values ranged from 8.73 (Trinidad) to 1.57 (The Bahamas, Turks and Caicos Islands). All four countries that have documented occurrences of laboratory confirmed rabid bats were ranked highest (Trinidad and Tobago, Grenada, Cuba, Dominican Republic), as well as Haiti. The top five highest risk countries that currently have no reports of bat rabies include St. Vincent and the Grenadines, Jamaica, Puerto Rico, the Cayman Islands, and Dominica. This study reviews the inter-island movement potential of bats, designates areas of high risk for bat-associated rabies within the Caribbean islands, and demonstrates a need for further surveillance efforts in bat populations within islands that self-declare as rabies free. Full article

We report mortality events in a group of 123 common vampire bats (Desmodus rotundus) captured in México and housed for a rabies vaccine efficacy study in Madison, Wisconsin. Bat mortalities occurred in México and Wisconsin, but rabies cases reported herein are only those that occurred after arrival in Madison (n = 15). Bats were confirmed positive for rabies virus (RABV) by the direct fluorescent antibody test. In accordance with previous reports, we observed long incubation periods (more than 100 days), variability in clinical signs prior to death, excretion of virus in saliva, and changes in rabies neutralizing antibody (rVNA) titers post-infection. We observed that the furious form of rabies (aggression, hyper-salivation, and hyper-excitability) manifested in three bats, which has not been reported in vampire bat studies since 1936. RABV was detected in saliva of 5/9 bats, 2–5 days prior to death, but was not detected in four of those bats that had been vaccinated shortly after exposure. Bats from different capture sites were involved in two separate outbreaks, and phylogenetic analysis revealed differences in the glycoprotein gene sequences of RABV isolated from each event, indicating that two different lineages were circulating separately during capture at each site. Full article

Antimicrobial resistance (AMR) is the major issue posing a serious global health threat. Low- and middle-income countries are likely to be the most affected, both in terms of impact on public health and economic burden. Recent studies highlighted the role of resistance networks on the transmission of AMR organisms, with this network being driven by complex interactions between clinical (e.g., human health, animal husbandry and veterinary medicine) and other components, including environmental factors (e.g., persistence of AMR in wastewater). Many studies have highlighted the role of wastewater as a significant environmental reservoir of AMR as it represents an ideal environment for AMR bacteria (ARB) and antimicrobial resistant genes (ARGs) to persist. Although the treatment process can help in removing or reducing the ARB load, it has limited impact on ARGs. ARGs are not degradable; therefore, they can be spread among microbial communities in the environment through horizontal gene transfer, which is the main resistance mechanism in most Gram-negative bacteria. Here we analysed the recent literature to highlight the contribution of wastewater to the emergence, persistence and transmission of AMR under different settings, particularly those associated with mass gathering events (e.g., Hajj and Kumbh Mela). Full article

Fox rabies has been eliminated from vast areas of West and Central Europe, but cases still occur in the Balkans. Oral vaccination is an effective method for reducing the incidence of the disease in wildlife, but it requires monitoring if bait density is adequate for the density of the wildlife reservoir. We developed a methodology to evaluate the effectiveness of aerial vaccination campaigns conducted in Montenegro during autumn 2011 and spring 2012. The effectiveness of the vaccination campaign was assessed by (i) estimating the density of baits, (ii) estimating the distribution of the red fox, (iii) identifying critical areas of insufficient bait density by combining both variables. Although the two vaccination campaigns resulted in 45% and 47% of the country’s total area not reaching recommended density of 20 baits/km², the consecutive delivery of both campaigns reduced these “gaps” to 6%. By combining bait and reservoir density data, we were able to show that bait density was lower than fox density in only 5% of Montenegro’s territory. The methodology described can be used for real-time evaluation of aerial vaccine delivery campaigns, to identify areas with insufficient bait densities. Full article

Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP) because it provides passive immunity to prevent this otherwise inescapably fatal disease in Category III exposed patients. Even with decades of development, RIG products are still criticized for their high cost, lot-to-lot variation, and potential safety issues. They remain largely unattainable in most developing regions of the world, where demand is highest. In recent years, monoclonal antibodies (MAbs) have become widely accepted as safer and more cost-effective alternatives to RIG products. As an example, SYN023 is a 1:1 cocktail of two humanized anti-rabies MAbs previously shown to display extensive neutralizing capabilities. Here, we further assessed the efficacy of SYN023 in animal models of rabies, and found that SYN023 afforded protection equal to a standard dose of human RIG (HRIG) at 0.03 mg/kg in Syrian hamsters and 0.1 mg/kg in beagles. Potential interference with vaccine-induced immunity was analyzed for the MAbs at these concentrations. While individual MAbs did not interfere with vaccine response, SYN023 at dosages of 0.1 mg/kg and above resulted in reduced neutralizing antibody titers similar to HRIG. Thus, the in vivo characterization of SYN023 supports its utility in human rabies PEP as an efficacious alternative to RIG products. Full article

Early-onset neonatal sepsis (EOS) is a major cause of neonatal death and long-term neurodevelopmental disabilities among survivors. The common pathogens causing EOS are group B streptococcus (GBS) and Escherichia coli. Haemophilus influenzae (H. influenzae) is a Gram-negative coccobacillus that can cause severe invasive disease and can be divided into either typeable or non-typeable strains. H. influenzae serotype b (Hib) is the most virulent and the major cause of bacterial meningitis in young children prior to routine immunization against Hib. Hib infection rates have dramatically reduced since then. However, a number of studies have reported an increasing incidence of non-typeable H. influenzae (NTHi) sepsis in neonates worldwide and concluded that pregnant women may have an increased risk to invasive NTHi disease with poor pregnancy outcomes. We present a case of fulminant neonatal sepsis caused by NTHi in an extremely preterm infant and discuss potential preventative measures to reduce its re-emergence. Full article

The twentieth century ended with human African trypanosomiasis (HAT) epidemics raging across many parts of Africa. Resistance to existing drugs was emerging, and many programs aiming to contain the disease had ground to a halt, given previous success against HAT and the competing priorities associated with other medical crises ravaging the continent. A series of dedicated interventions and the introduction of innovative routes to develop drugs, involving Product Development Partnerships, has led to a dramatic turnaround in the fight against HAT caused by Trypanosoma brucei gambiense. The World Health Organization have been able to optimize the use of existing tools to monitor and intervene in the disease. A promising new oral medication for stage 1 HAT, pafuramidine maleate, ultimately failed due to unforeseen toxicity issues. However, the clinical trials for this compound demonstrated the possibility of conducting such trials in the resource-poor settings of rural Africa. The Drugs for Neglected Disease initiative (DNDi), founded in 2003, has developed the first all oral therapy for both stage 1 and stage 2 HAT in fexinidazole. DNDi has also brought forward another oral therapy, acoziborole, potentially capable of curing both stage 1 and stage 2 disease in a single dosing. In this review article, we describe the remarkable successes in combating HAT through the twenty first century, bringing the prospect of the elimination of this disease into sight. Full article

Current anti-trypanosomal therapies suffer from problems of longer treatment duration, toxicity and inadequate efficacy, hence there is a need for safer, more efficacious and ‘easy to use’ oral drugs. Previously, we reported the discovery of the triazolopyrimidine (TP) class as selective kinetoplastid proteasome inhibitors with in vivo efficacy in mouse models of leishmaniasis, Chagas Disease and African trypanosomiasis (HAT). For the treatment of HAT, development compounds need to have excellent penetration to the brain to cure the meningoencephalic stage of the disease. Here we describe detailed biological and pharmacological characterization of triazolopyrimidine compounds in HAT specific assays. The TP class of compounds showed single digit nanomolar potency against Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense strains. These compounds are trypanocidal with concentration-time dependent kill and achieved relapse-free cure in vitro. Two compounds, GNF6702 and a new analog NITD689, showed favorable in vivo pharmacokinetics and significant brain penetration, which enabled oral dosing. They also achieved complete cure in both hemolymphatic (blood) and meningoencephalic (brain) infection of human African trypanosomiasis mouse models. Mode of action studies on this series confirmed the 20S proteasome as the target in T. brucei. These proteasome inhibitors have the potential for further development into promising new treatment for human African trypanosomiasis. Full article

Despite the World Health Organization recommending the use of rapid molecular tests for diagnosing tuberculosis (TB), uptake has been limited, partially due to high cartridge costs. Other infectious disease programs pool specimens to save on diagnostic test costs. We tested a sputum pooling strategy as part of a TB case finding program using Xpert MTB/RIF Ultra (Ultra). All persons were tested with Ultra individually, and their remaining specimens were also grouped with 3–4 samples for testing in a pooled sample. Individual and pooled testing results were compared to see if people with TB would have been missed when using pooling. We assessed the potential cost and time savings which different pooling strategies could achieve. We tested 584 individual samples and also grouped them in 153 pools for testing separately. Individual testing identified 91 (15.6%) people with positive Ultra results. One hundred percent of individual positive results were also found to be positive by the pooling strategy. Pooling would have saved 27% of cartridge and processing time. Our results are the first to use Ultra in a pooled approach for TB, and demonstrate feasibility in field conditions. Pooling did not miss any TB cases and can save time and money. The impact of pooling is only realized when yield is low. Full article

To improve tuberculosis (TB) care among individuals attending a private tertiary care hospital in Vietnam, an innovative private sector engagement model was implemented from June to December 2018. This included: (i) Active facility-based screening of all adults for TB symptoms (and chest x-ray (CXR) for those with symptoms) by trained and incentivized providers, with on-site diagnostic testing or transport of sputum samples, (ii) a mobile application to reduce dropout in the care cascade and (iii) enhanced follow-up care by community health workers. We conducted a cohort study using project and routine surveillance data for evaluation. Among 52,078 attendees, 368 (0.7%) had symptoms suggestive of TB and abnormalities on CXR. Among them, 299 (81%) were tested and 103 (34.4%) were diagnosed with TB. In addition, 195 individuals with normal CXR were indicated for TB testing by attending clinicians, of whom, seven were diagnosed with TB. Of the 110 TB patients diagnosed, 104 (95%) were initiated on treatment and 97 (93%) had a successful treatment outcome. Given the success of this model, the National TB Programme is considering to scale it up nationwide after undertaking a detailed cost-effectiveness analysis. Full article

We carried out a baseline survey of cattle in Kaberamaido district, in the context of controlling the domestic animal reservoir of Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) towards elimination. Cattle blood was subjected to capillary tube centrifugation followed by measurement of the packed cell volume (PCV) and examination of the buffy coat area for motile trypanosomes. Trypanosomes were detected in 561 (21.4%) out of 2621 cattle screened by microscopy. These 561 in addition to 724 apparently trypanosome negative samples with low PCVs (≤25%) were transported to the laboratory and tested by PCR targeting the trypanosomal Internal Transcribed Spacer (ITS-1) as well as suspect Tick-Borne Diseases (TBDs) including Anaplasmamosis, Babesiosis, and Theileriosis. PCR for Anaplasma sp yielded the highest number of positive animals (45.2%), followed by Trypanosoma sp (44%), Theileria sp (42.4%) and Babesia (26.3%); multiple infections were a common occurrence. Interestingly, 373 (29%) of these cattle with low PCVs were negative by PCR, pointing to other possible causes of aneamia, such as helminthiasis. Among the trypanosome infections classified as T. brucei by ITS-PCR, 5.5% were positive by SRA PCR, and were, therefore, confirmed as T. b. rhodesiense. Efforts against HAT should therefore consider packages that address a range of conditions. This may enhance acceptability and participation of livestock keepers in programs to eliminate this important but neglected tropical disease. In addition, we demonstrated that cattle remain an eminent reservoir for T. b. rhodesiense in eastern Uganda, which must be addressed to sustain HAT elimination. Full article

The work began with the screening of a library of 700,000 small molecules for inhibitors of Trypanosoma brucei growth (a phenotypic screen). The resulting set of 1035 hit compounds was reviewed by a team of medicinal chemists, leading to the nomination of 17 chemically distinct scaffolds for further investigation. The first triage step was the assessment for brain permeability (looking for brain levels at least 20% of plasma levels) in order to optimize the chances of developing candidates for treating late-stage human African trypanosomiasis. Eleven scaffolds subsequently underwent hit-to-lead optimization using standard medicinal chemistry approaches. Over a period of six years in an academic setting, 1539 analogs to the 11 scaffolds were synthesized. Eight scaffolds were discontinued either due to insufficient improvement in antiparasitic activity (5), poor pharmacokinetic properties (2), or a slow (static) antiparasitic activity (1). Three scaffolds were optimized to the point of curing the acute and/or chronic T. brucei infection model in mice. The progress was accomplished without knowledge of the mechanism of action (MOA) for the compounds, although the MOA has been discovered in the interim for one compound series. Studies on the safety and toxicity of the compounds are planned to help select candidates for potential clinical development. This research demonstrates the power of the phenotypic drug discovery approach for neglected tropical diseases. Full article

The objectives of this paper are to provide a review of the author’s personal experiences working in culturally diverse environments and to emphasize the importance of recognizing the social determinants of health. While some determinants of health are modifiable others are not, in addition it is emphasized that cultural safety in delivering health care is crucial if services provided are to be appropriate and acceptable to health care seekers. Cultural sensitivity is needed if one is to make a change in health outcomes in culturally diverse environments. The development and delivery of culturally safe services is more acceptable to community members and is important if a difference is to be made in health inequities. Training in delivering culturally safe services should include both theoretical and practical components. Practical training should be conducted under supervision in remote settings so that trainees appreciate what their clients experience on a daily basis. Culturally “unsafe” clinical service has serious adverse effects. This commentary discusses the above factors and provides example cases from the author’s own career of where such factors have affected the health of individuals or groups. Full article

Early detection of pediatric eye problems can prevent future vision loss. This study was to estimate the prevalence of common eye problems among infants born in a resource-constrained emergency setting with a broader aim to prevent future vision loss or blindness among them through early detection and referral. We conducted a cross-sectional survey among 670 infants (0–59 days old) born in Rohingya refugee camps in Bangladesh between March and June of 2019. The most common eye problem found was watering from the eye and accumulation of discharge by which 14.8% of the children were suffering (95% CI: 12.2–17.7). More than 5% of the infants had visual inattention (95% CI: 3.5–7.0), and 4% had redness in their eyes (95% CI: 2.7–5.8). Only 1.9% of infants (95% CI: 1–3.3) had whitish or brown eyeballs, and 1.8% of children might have whitish pupillary reflex (95% CI: 0.9–3.1). None of the eye problems was associated with the gender of the infants. The prevalent eye problems demand eye care set up for the screening of eye problems in the camps with proper referral and availability of referral centres with higher service in the districts. Full article

Schistosomiasis affects about 240 million people worldwide and Schistosoma mansoni alone affects over 54 million people leaving 400 million at-risk especially in Sub Saharan Africa (SSA). About 20 million people are currently suffering from complications of chronic S. mansoni infection and up to 42% of those infected have been found with periportal fibrosis (PPF). About 0.2 million deaths are attributed to chronic S. mansoni every year, which is mainly due to varices. Death occurs in up to 29% of those who present late with bleeding varices even with the best available in-hospital care. The diagnosis of varices before incident bleeding could potentially improve the outcome of this subgroup of patients is SSA. However, there is no prior review which has ever evaluated this issue detailing the magnitude and outcome of varices following available treatment modalities among patients with Schistosoma PPF in SSA. This review summarizes the available literature on this matter and exposes potential practical gaps that could be bridged to maximize the long-term outcome of patients with S. mansoni related PPF in SSA. A total of 22 studies were included in this review. The average prevalence of varices was 82.1% (SD: 29.6; range: 11.1%–100%) among patients with PPF. Late diagnosis of varices was frequent with average bleeding and mortality of 71.2% (SD: 36.5; range: 4.3%–100.0%) and 13.6% (SD: 9.9; range: 3.5%–29%), respectively. Predictors were reported in seven (31.8%) studies including platelet count to splenic diameter ratio (PSDR) for prediction large varices in one study. Active S. mansoni infection was very prevalent, (mean: 69.9%; SD: 24.4; range: 29.2–100.0%). Praziquantel could reverse PPF and use of non-selective B-blockers reduced both rebleeding and mortality. Use of sclerotherapy for secondary prevention of variceal bleeding was associated with high rebleeding and mortality rates. Conclusions: This review shows that varices due to schistosomal PPF are a big problem in SSA. However, patients are often diagnosed late with fatal bleeding varices. No study had reported a clinical tool that could be useful in early diagnosis of patients with varices and no study reported on primary and effective secondary prevention of bleeding and its outcome. Regular screening for S. mansoni and the provision of Praziquantel (PZQ) is suggested in this review. More studies are required to bridge these practical gaps in Sub Saharan Africa. Full article

In Myanmar from July 2018, as a pilot project in 32 townships, all tuberculosis (TB) patients aged ≥40 years were eligible for diabetes mellitus (DM) screening by random blood sugar (RBS) and all DM patients attending hospitals were eligible for TB screening. We assessed the bidirectional screening coverage of target groups through a cross sectional study involving secondary analysis of routine program data. From January to March 2019, of the 5202 TB patients enrolled, 48% were aged ≥40 years. Of those aged ≥40 years, 159 (6%) were known to have DM, and the remaining 2343 with unknown DM status were eligible for DM screening. Of these, 1280 (55%) were screened and 139 (11%) had high RBS values (≥200 mg/dL, as defined by the national program). There was no information on whether patients with high RBS values were linked to DM care. Of the total 8198 DM patients attending hospitals, 302 (3.7%) patients were tested for sputum smear and 147 (1.7%) were diagnosed with TB. In conclusion, only half of the eligible TB patients were screened for DM and the yield of TB cases among screened DM patients was high. There is an urgent need for improving and scaling up bidirectional screening in the country. Full article

Antimicrobial resistance (AMR) is a global public health issue. Upper respiratory tract infections (URTIs) are common illnesses during Hajj, for which antibiotics are often inappropriately prescribed. Hajj healthcare workers’ (HCW) knowledge, attitudes and perceptions (KAP) about AMR and antibiotic use for URTIs are not known. We conducted a survey among HCWs during Hajj to explore their KAP regarding antibiotic use for URTIs in pilgrims. Electronic or paper-based surveys were distributed to HCWs during the Hajj in 2016 and 2017. A total of 85 respondents aged 25 to 63 (median 40) years completed the surveys. Most participants were male (78.8%) and were physicians by profession (95.3%). Around 85% and 19% of respondents claimed to have heard about AMR and antimicrobial stewardship programs, respectively, among whom most had obtained their knowledge during their qualification. Implementation of URTI treatment guidelines was very low. In conclusion, HCWs at Hajj have significant knowledge gaps regarding AMR, often do not use standard clinical criteria to diagnose URTIs and display a tendency to prescribe antibiotics for URTIs. Full article