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  • Decentralised hepatitis C testing and treatment in rural Cambodia: evaluation of a simplified service model integrated in an existing public health system.

    Zhang, M; O'Keefe, D; Craig, J; Samley, K; Bunreth, V; Jolivet, P; Balkan, S; Marquardt, T; Dousset, JP; Le Paih, M (Elsevier, 2021-03-18)
    Background: Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement a simplified model of HCV care via decentralised health services within a rural health operational district in Battambang province, Cambodia. Methods: The study cohort included adult residents (≥18 years) of the health operational district of Moung Russei who were voluntarily screened at 13 local health centres. Serology testing was done by a rapid diagnostic test using SD Bioline HCV (SD Bioline HCV, Standard Diagnostics, South Korea) with capillary blood. HCV viral load testing was done by GeneXpert (Cepheid, Sunnyvale, CA, USA). Viraemic patients (HCV viral load ≥10 IU/mL) received pretreatment assessment by a general physician and minimal treatment evaluation tests at the health operational district referral hospital. Viraemic patients who did not have additional complications received all HCV care follow-up at the local health centres, provided by nursing staff, and patients who had decompensated cirrhosis, previously treated with a direct-acting antiviral, HBV co-infection, or other comorbidities requiring observation continued receiving care at the referral hospital with a general physician. Patients deemed eligible for treatment were prescribed oral sofosbuvir (400 mg) and daclatasvir (60 mg) once a day for 12 weeks, or 24 weeks for patients with decompensated cirrhosis or those previously treated with a direct-acting antiviral. HCV cure was defined as sustained virological response at 12 weeks after treatment (HCV viral load <10 IU/mL). Patients were assessed for serious and non-serious adverse events at any time between treatment initiation and 12 weeks post-treatment testing. Findings: Between March 12, 2018, and Jan 18, 2019, 10 425 residents (ie, 7·6% of the estimated 136 571 adults in the health operational district of Moung Russei) were screened. Of those patients screened, the median age was 44 years (IQR 31-55) and 778 (7·5%) were HCV-antibody positive. 761 (97·8%) of 778 antibody-positive patients received HCV viral load testing, and 540 (71·0%) of those tested were HCV viraemic. Among these 540 patients, linkage to treatment and follow-up care was high, with 533 (98·7%) attending a baseline consultation at the HCV clinic, of whom 530 (99·4%) initiated treatment. 485 (91·5%) of 530 patients who initiated treatment received follow-up at a health centre and 45 (8·5%) were followed up at the referral hospital. Of the 530 patients who initiated direct-acting antiviral therapy, 515 (97·2%) completed treatment. Subsequently, 466 (90·5%) of 515 patients completed follow-up, and 459 (98·5%) of 466 achieved a sustained virological response at 12 weeks after treatment. Two (0·4%) adverse events (fatigue [n=1] and stomach upset [n=1]) and five (0·9%) serious adverse events (infection [n=2], cardiovascular disease [n=1], and panic attack [n=1], with data missing for one of the causes of serious adverse events) were reported among patients who initiated treatment. All serious adverse events were deemed to be unrelated to therapy. Interpretation: This pilot project showed that a highly simplified, decentralised model of HCV care can be integrated within a rural public health system in a low-income or middle-income country, while maintaining high patient retention, treatment efficacy, and safety. The project delivered care via accessible, decentralised primary health centres, using non-specialist clinical staff, thereby enhancing the efficient use of limited resources and maximising the potential to test and treat individuals living with HCV infection.
  • Decentralized hepatitis C testing and treatment in rural Cambodia: evaluation of a simplified service model integrated in an existing public health system

    Zhang, M; O'Keefe, D; Craig, J; Samley, K; Bunreth, V; Jolivet, P; Balkan, S; Marquardt, T; Dousset, JP; Le Paih, M (Elsevier, 2021-03-18)
    Background Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement a simplified model of HCV care via decentralised health services within a rural health operational district in Battambang province, Cambodia. Methods The study cohort included adult residents (≥18 years) of the health operational district of Moung Russei who were voluntarily screened at 13 local health centres. Serology testing was done by a rapid diagnostic test using SD Bioline HCV (SD Bioline HCV, Standard Diagnostics, South Korea) with capillary blood. HCV viral load testing was done by GeneXpert (Cepheid, Sunnyvale, CA, USA). Viraemic patients (HCV viral load ≥10 IU/mL) received pretreatment assessment by a general physician and minimal treatment evaluation tests at the health operational district referral hospital. Viraemic patients who did not have additional complications received all HCV care follow-up at the local health centres, provided by nursing staff, and patients who had decompensated cirrhosis, previously treated with a direct-acting antiviral, HBV co-infection, or other comorbidities requiring observation continued receiving care at the referral hospital with a general physician. Patients deemed eligible for treatment were prescribed oral sofosbuvir (400 mg) and daclatasvir (60 mg) once a day for 12 weeks, or 24 weeks for patients with decompensated cirrhosis or those previously treated with a direct-acting antiviral. HCV cure was defined as sustained virological response at 12 weeks after treatment (HCV viral load <10 IU/mL). Patients were assessed for serious and non-serious adverse events at any time between treatment initiation and 12 weeks post-treatment testing. Findings Between March 12, 2018, and Jan 18, 2019, 10 425 residents (ie, 7·6% of the estimated 136 571 adults in the health operational district of Moung Russei) were screened. Of those patients screened, the median age was 44 years (IQR 31–55) and 778 (7·5%) were HCV-antibody positive. 761 (97·8%) of 778 antibody-positive patients received HCV viral load testing, and 540 (71·0%) of those tested were HCV viraemic. Among these 540 patients, linkage to treatment and follow-up care was high, with 533 (98·7%) attending a baseline consultation at the HCV clinic, of whom 530 (99·4%) initiated treatment. 485 (91·5%) of 530 patients who initiated treatment received follow-up at a health centre and 45 (8·5%) were followed up at the referral hospital. Of the 530 patients who initiated direct-acting antiviral therapy, 515 (97·2%) completed treatment. Subsequently, 466 (90·5%) of 515 patients completed follow-up, and 459 (98·5%) of 466 achieved a sustained virological response at 12 weeks after treatment. Two (0·4%) adverse events (fatigue [n=1] and stomach upset [n=1]) and five (0·9%) serious adverse events (infection [n=2], cardiovascular disease [n=1], and panic attack [n=1], with data missing for one of the causes of serious adverse events) were reported among patients who initiated treatment. All serious adverse events were deemed to be unrelated to therapy. Interpretation This pilot project showed that a highly simplified, decentralised model of HCV care can be integrated within a rural public health system in a low-income or middle-income country, while maintaining high patient retention, treatment efficacy, and safety. The project delivered care via accessible, decentralised primary health centres, using non-specialist clinical staff, thereby enhancing the efficient use of limited resources and maximising the potential to test and treat individuals living with HCV infection.
  • Early onset of neurological features differentiates two outbreaks of Lassa fever in Ebonyi state, Nigeria during 2017-2018.

    Chika-Igwenyi, NM; Harrison, RE; Psarra, C; Gil Cuesta, J; Gulamhusein, M; Onwe, EO; Onoh, RC; Unigwe, US; Ajayi, NA; Nndadozie, UU; et al. (Public Library of Science, 2021-03-08)
    Lassa fever (LF) is an acute viral haemorrhagic illness with various non-specific clinical manifestations. Neurological symptoms are rare at the early stage of the disease, but may be seen in late stages, in severely ill patients.The aim of this study was to describe the epidemiological evolution, socio-demographic profiles, clinical characteristics, and outcomes of patients seen during two Lassa fever outbreaks in Ebonyi State, between December 2017 and December 2018. Routinely collected clinical data from all patients admitted to the Virology Centre of the hospital during the period were analysed retrospectively. Out of a total of 83 cases, 70(84.3%) were RT-PCR confirmed while 13 (15.7%) were probable cases. Sixty-nine (83.1%) patients were seen in outbreak 1 of whom 53.6% were urban residents, while 19%, 15%, and 10% were farmers, students and health workers respectively. There were 14 (16.8%) patients, seen in second outbreak with 92.9% rural residents. There were differences in clinical symptoms, signs and laboratory findings between the two outbreaks. The case fatality rates were 29.9% in outbreak 1 and 85.7% for outbreak 2. Neurological features and abnormal laboratory test results were associated with higher mortality rate, seen in outbreak 2. This study revealed significant differences between the two outbreaks. Of particular concern was the higher case fatality during the outbreak 2 which may be from a more virulent strain of the Lassa virus. This has important public health implications and further molecular studies are needed to better define its characteristics.
  • Hepatitis C viraemic and seroprevalence and risk factors for positivity in Northwest Cambodia: a household cross-sectional serosurvey.

    Lynch, E; Falq, G; Sun, C; Bunchhoeung, PDT; Huerga, H; Loarec, A; Dousset, JP; Marquardt, T; Le Paih, M; Maman, D (BMC, 2021-02-26)
    Background: Despite a dramatic reduction in HCV drug costs and simplified models of care, many countries lack important information on prevalence and risk factors to structure effective HCV services. Methods: A cross-sectional, multi-stage cluster survey of HCV seroprevalence in adults 18 years and above was conducted, with an oversampling of those 45 years and above. One hundred forty-seven clusters of 25 households were randomly selected in two sets (set 1=24 clusters ≥18; set 2=123 clusters, ≥45). A multi-variable analysis assessed risk factors for sero-positivity among participants ≥45. The study occurred in rural Moung Ruessei Health Operational District, Battambang Province, Western Cambodia. Results: A total of 5098 individuals and 3616 households participated in the survey. The overall seroprevalence was 2.6% (CI95% 2.3-3.0) for those ≥18 years, 5.1% (CI95% 4.6-5.7) for adults ≥ 45 years, and 0.6% (CI95% 0.3-0.9) for adults 18-44. Viraemic prevalence was 1.9% (CI95% 1.6-2.1), 3.6% (CI95% 3.2-4.0), and 0.5% (CI95% 0.2-0.8), respectively. Men had higher prevalence than women: ≥18 years male seroprevalence was 3.0 (CI95% 2.5-3.5) versus 2.3 (CI95% 1.9-2.7) for women. Knowledge of HCV was poor: 64.7% of all respondents and 57.0% of seropositive participants reported never having heard of HCV. Risk factor characteristics for the population ≥45 years included: advancing age (p< 0.001), low education (higher than secondary school OR 0.7 [95% CI 0.6-0.8]), any dental or gum treatment (OR 1.6 [95% CI 1.3-1.8]), historical routine medical care (medical injection after 1990 OR 0.7 [95% CI 0.6-0.9]; surgery after 1990 OR 0.7 [95% CI0.5-0.9]), and historical blood donation or transfusion (blood donation after 1980 OR 0.4 [95% CI 0.2-0.8]); blood transfusion after 1990 OR 0.7 [95% CI 0.4-1.1]). Conclusions: This study provides the first large-scale general adult population prevalence data on HCV infection in Cambodia. The results confirm the link between high prevalence and age ≥45 years, lower socio-economic status and past routine medical interventions (particularly those received before 1990 and 1980). This survey suggests high HCV prevalence in certain populations in Cambodia and can be used to guide national and local HCV policy discussion.
  • AI-based mobile application to fight antibiotic resistance.

    Pascucci, M; Royer, G; Adamek, J; Al Asmar, M; Aristizabal, D; Blanche, L; Bezzarga, A; Boniface-Chang, G; Brunner, A; Curel, C; et al. (Springer Nature, 2021-02-19)
    Antimicrobial resistance is a major global health threat and its development is promoted by antibiotic misuse. While disk diffusion antibiotic susceptibility testing (AST, also called antibiogram) is broadly used to test for antibiotic resistance in bacterial infections, it faces strong criticism because of inter-operator variability and the complexity of interpretative reading. Automatic reading systems address these issues, but are not always adapted or available to resource-limited settings. We present an artificial intelligence (AI)-based, offline smartphone application for antibiogram analysis. The application captures images with the phone's camera, and the user is guided throughout the analysis on the same device by a user-friendly graphical interface. An embedded expert system validates the coherence of the antibiogram data and provides interpreted results. The fully automatic measurement procedure of our application's reading system achieves an overall agreement of 90% on susceptibility categorization against a hospital-standard automatic system and 98% against manual measurement (gold standard), with reduced inter-operator variability. The application's performance showed that the automatic reading of antibiotic resistance testing is entirely feasible on a smartphone. Moreover our application is suited for resource-limited settings, and therefore has the potential to significantly increase patients' access to AST worldwide.
  • Novel transdisciplinary methodology for cross-sectional analysis of snakebite epidemiology at national scale.

    Alcoba, G; Ochoa, C; Martins, SB; Ruiz de Castaneda, R; Bolon, I; Wanda, F; Comte, E; Subedi, M; Shah, B; Ghimire, A; et al. (Public Library of Science, 2021-02-12)
    Background: Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal. Methodology/principal findings: We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility. Conclusions/significance: This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.
  • Cost and cost-effectiveness of a real-world HCV treatment program among HIV-infected individuals in Myanmar.

    Marquez, LK; Chaillon, A; Soe, KP; Johnson, DC; Zosso, JM; Incerti, A; Loarec, A; Nguyen, A; Walker, JG; Mafirakureva, N; et al. (BMJ Publishing Group, 2021-02-01)
    Introduction: Over half of those hepatitis C virus (HCV)/HIV coinfected live in low-income and middle-income countries, and many remain undiagnosed or untreated. In 2016, Médecins Sans Frontières (MSF) established a direct-acting antiviral (DAA) treatment programme for people HCV/HIV coinfected in Myanmar. The purpose of our study was to evaluate the real-world cost and cost-effectiveness of this programme, and potential cost-effectiveness if implemented by the Ministry of Health (MoH). Methods: Costs (patient-level microcosting) and treatment outcomes were collected from the MSF prospective cohort study in Dawei, Myanmar. A Markov model was used to assess cost-effectiveness of the programme compared with no HCV treatment from a health provider perspective. Estimated lifetime and healthcare costs (in 2017 US$) and health outcomes (in disability-adjusted life-years (DALYs)) were simulated to calculate the incremental cost-effectiveness ratio (ICER), compared with a willingness-to-pay threshold of per capita Gross Domestic Product in Myanmar ($1250). We evaluated cost-effectiveness with updated quality-assured generic DAA prices and potential cost-effectiveness of a proposed simplified treatment protocol with updated DAA prices if implemented by the MoH. Results: From November 2016 to October 2017, 122 with HIV/HCV-coinfected patients were treated with DAAs (46% with cirrhosis), 96% (n=117) achieved sustained virological response. Mean treatment costs were $1229 (without cirrhosis) and $1971 (with cirrhosis), with DAA drugs being the largest contributor to cost. Compared with no treatment, the program was cost-effective (ICER $634/DALY averted); more so with updated prices for quality-assured generic DAAs (ICER $488/DALY averted). A simplified treatment protocol delivered by the MoH could be cost-effective if associated with similar outcomes (ICER $316/DALY averted). Conclusions: Using MSF programme data, the DAA treatment programme for HCV among HIV-coinfected individuals is cost-effective in Myanmar, and even more so with updated DAA prices. A simplified treatment protocol could enhance cost-effectiveness if further rollout demonstrates it is not associated with worse treatment outcomes.
  • Seizure activity and anion gap metabolic acidosis secondary to adverse effect of nalidixic acid—a case report

    Galvin, M; Al Qaisy, MS; Cajazeiro, J (Oxford University Press, 2021-01-12)
    Nalidixic acid is a commonly prescribed treatment for suspected dysentery in Middle Eastern populations. We describe a case of convulsions resulting from a single dose of nalidixic acid in a previously healthy two-month-old child in Northern Iraq who was being treated for a diarrhoeal illness. The child presented to us with new onset seizures, irritability, and acidaemia. Nalidixic acid was thought to be responsible after the exclusion of other potential causes of seizures. Symptoms resolved by treatment with intravenous (IV) diazepam, and cessation of nalidixic acid, and the child recovered fully and was discharged home neurologically intact after two days of observation. In regions where it is commonly prescribed, such as Northern Iraq, nalidixic acid should be considered as a cause of convulsions in any seizing child who has been exposed to the drug. Furthermore, quinolones such as nalidixic acid are contraindicated in children < 3 months of age.
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    Mashe, T; Leekitcharoenphon, P; Mtapuri-Zinyowera, S; Kingsley, RA; Robertson, V; Tarupiwa, A; Kock, MM; Makombe, EP; Chaibva, BV; Manangazira, P; et al. (Oxford University Press, 2020-12-21)
    Background Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control. Objectives To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics. Methods : A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis. Results A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (4.3.1.1), with a maximum pair-wise distance of 22 SNPs. Conclusions This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 4.3.1.1 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.
  • Hemophagocytic Lymphohistiocytosis Masquerading as Alcoholic Hepatitis

    Abulaimon, S; Abushalha, K; Reddymasu, S; Teruya, B; Natarajan, N (Lippincott, Williams & Wilkins, 2020-12-10)
    Hemophagocytic lymphohistiocytosis is a syndrome characterized by excessive immune activation. Timely diagnosis can be challenging, and prompt treatment is the only hope for survival. We present an adult patient with a history of alcohol dependence, who presented with fatigue, bilateral lower extremity edema, and orange-colored urine. Clinical workup revealed abnormal liver function tests, elevated ferritin, cytopenia, and lymphadenopathy. Eventually, he was diagnosed with hemophagocytic lymphohistiocytosis. This case report encourages gastroenterologists to maintain a high index of suspicion when a patient presents with liver failure, hyperferritinemia, and cytopenia because they may be the first healthcare professionals to evaluate these patients.
  • Another form of Lassa fever? Early neurological symptoms and high mortality reveal differences in two outbreaks in Ebonyi State, Nigeria 2017–2019

    Chika-Igwenyi, N; Harrison, RE; Unigwe, U; Psarra, C; Onwe Ogah, E; Ajayi, N; Onoh, R; Ugwu, C; Reid, A (International Society for Infectious Diseases, 2020-12-01)
    Background: Lassa fever (LF) is an acute viral haemorrhagic illness with various clinical manifestations. Neurological symptoms are not commonly present at the early stage of the disease; however, early manifestation of central nervous system features depicts poor prognostication. In Ebonyi state, an unusual pattern was observed between two outbreaks with patients presenting early neurological symptoms and a high mortality rate in the second outbreak. The study described the epidemiological evolution, socio-demographic profiles, clinical characteristics and patients’ outcomes. Methods and materials: A retrospective analytic analysis of routinely collected clinical data was conducted of all confirmed and probable LF patients admitted to the Virology Centre of the AEFUTHA in Ebonyi State, December 2017 to January 2019. Results: In a total of 83 cases, 70 were RT-PCR confirmed and 13 probable cases. In outbreak 1, 69 were seen with 53.6% being urban residents, 19% farmers, 15% students, and 10% health workers. Fourteen cases were seen in outbreak 2 with 92.9% rural residents, 58.3% being farmers and 49.9% students. There were differences in clinical and laboratory signs and symptoms between the two outbreaks with neurological symptoms present 43% of the time in outbreak 1 and 93% in outbreak 2 (p = 0.001), with a shorter time of onset for these symptoms in outbreak 2. The mortality rate was 85.7% in outbreak 2 versus 29.9% in outbreak 1 (p < 0.001). Patients with neurological symptoms, who were more common in outbreak 2 had a RR of dying of 8.5 compared to those without. Conclusion: This study revealed a different form of LF that is of great concern due to its high mortality rate. Further studies are needed to better define its characteristics.
  • Torture-induced hand electrical injury: A case report

    Alqassab, S; Mathieu, L; We regret that this article is behind a paywall. (Elsevier, 2020-11-21)
    The authors report an unusual case of hand electrical injury related to torture in a war refugee. The patient was referred for the reconstruction of bilateral hand function several years after being tortured. He presented with severe hand contractures combined with motor and sensory loss. After nonoptimal treatment in the acute period, the reconstruction options were limited by the delayed management. This unique clinical presentation can be explained by repetition of prolonged electrical shocks using a low-voltage current.
  • Dengue in Western Uganda: a prospective cohort of children presenting with undifferentiated febrile illness

    Boyce, RM; Collins, M; Muhindo, R; Nakakande, R; Ciccone, EJ; Grounds, S; Espinoza, D; Zhu, Y; Matte, M; Ntaro, M; et al. (BMC, 2020-11-11)
    Background The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. Methods Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. Results Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). Conclusions Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.
  • Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the “PI-POC” Trial

    Gaudenzi, G; Kumbakumba, E; Rasti, R; Nanjebe, D; Reu, P; Nyehangane, D; Martensson, A; Nassejje, M; Karlsson, J; Mzee, J; et al. (JMIR Publications, 2020-11-04)
    Background: A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
  • Perspectives from MSF snakebite programme implementation in Agok, Abyei region, South Sudan

    Said, M; Valdespino, E; Baba, SP; Lako, R; Malm, A; Gonzalez, A; Alcoba, G (South Sudan Medical Journal, 2020-11-01)
    Introduction: Snakebite is a neglected tropical disease affecting around five million people, causing more than 100,000 annual deaths, as well as serious disabilities; however, access to antivenom and high-quality programmatic care remain a global challenge. Objective: Due to the high burden of snakebite in South Sudan and the serious negative outcomes if left untreated, Médecins Sans Frontières (MSF) integrated snakebite care for the first time among its priorities and consolidated a programme in Agok Hospital. Method: We describe the history, implementation, and challenges of the MSF snakebite programme. Results: The number of snakebite patients at MSF Agok Hospital has increased each year. From 2013 to 2019, MSF treated 2,005 snakebite patients. In 2019 there were 527 snakebite admissions, 47% presented with severe envenomation, and one death. Puff adders, vipers and various cobras were identified. Agok Hospital gained understanding on the barriers and facilitators for the population to access care after a snakebite. MSF developed “snakebite diagnosis and treatment” algorithms, and provided clinical training, with the validation of national health authorities. Preventive activities were reinforced. Integration of surgical services was an essential programmatic aspect to monitor and treat complications. Challenges for implementation included a lack of easily available antivenoms in the international market. and the need of a strong supply chain and procurement systems. Conclusion: The delivery of healthcare towards snakebite patients can be successfully implemented when prioritized. Global efforts to improve access and quality of antivenoms and snakebite care could help removing Snakebite Envenoming from the Neglected Tropical Diseases list.
  • Cost-effectiveness of screening and treatment using direct-acting antivirals for chronic Hepatitis C virus in a primary care setting in Karachi, Pakistan

    Mafirakureva, N; Lim, AG; Khalid, GG; Aslam, K; Campbell, L; Zahid, H; Van den Bergh, R; Falq, G; Fortas, C; Wailly, Y; et al. (Wiley, 2020-10-14)
    abilistic sensitivity analyses (PSA). The ICER for implementing testing and treatment compared to no programme was US$450/DALY averted, with 100% of PSA runs falling below the per capita Gross Domestic Product threshold for cost-effective interventions for Pakistan (US$1,422). The ICER increased to US$532/DALY averted assuming national HCV seroprevalence (5.5% versus 33% observed in the intervention). If the cost of liver disease care was included (adapted from resource use data from Cambodia which has similar GDP to Pakistan), the ICER dropped to US$148/DALY, while it became cost-saving if a recently negotiated reduced drug cost of $75/treatment course was assumed (versus $282 in base-case) in addition to cost of liver disease care. In conclusion, screening and DAA treatment for HCV infection are expected to be highly cost-effective in Pakistan, supporting the expansion of similar screening and treatment programmes across Pakistan.
  • Outcomes of cholera and measles outbreak alerts in the Democratic Republic of Congo

    Makelele, JPK; Ade, S; Takarinda, KC; Manzi, M; Cuesta, JG; Acma, A; Yepez, MM; Mashak, M (International Union Against Tuberculosis and Lung Disease, 2020-09-21)
    Setting: In 1995, a rapid response project for humanitarian and medical emergencies, including outbreak responses, named ‘Pool d’Urgence Congo’ (PUC), was implemented in the Democratic Republic of Congo by Médecins Sans Frontières. Objective: To assess the outcomes of cholera and measles outbreak alerts that were received in the PUC surveillance system between 2016 and 2018. Design: This was a retrospective cross-sectional study. Results: Overall, 459 outbreak alerts were detected, respectively 69% and 31% for cholera and measles. Of these, 32% were actively detected and 68% passively detected. Most alerts (90%) required no intervention and 10% of alerts had an intervention. There were 25% investigations that were not carried out despite thresholds being met; 17% interventions were not performed, the main reported reason being PUC operational capacity was exceeded. Confirmed cholera and measles outbreaks that met an investigation threshold comprised respectively 90% and 76% of alerts; 59% of measles investigations were followed by a delayed outbreak response of 14 days (n = 10 outbreaks). Conclusion: Some alerts for cholera and measles outbreaks that were detected in the PUC system did not lead to a response even when required; the main reported reason was limited operational capacity to respond to all of them.
  • Estimation of Rift Valley fever virus spillover to humans during the Mayotte 2018–2019 epidemic

    Metras, R; Edmunds, WJ; Youssouffi, C; Dommergues, L; Fournie, G; Camacho, A; Funk, S; Cardinale, E; Le Godais, G; Combo, S; et al. (National Academy of Sciences., 2020-09-14)
    Rift Valley fever (RVF) is an emerging, zoonotic, arboviral hemorrhagic fever threatening livestock and humans mainly in Africa. RVF is of global concern, having expanded its geographical range over the last decades. The impact of control measures on epidemic dynamics using empirical data has not been assessed. Here, we fitted a mathematical model to seroprevalence livestock and human RVF case data from the 2018–2019 epidemic in Mayotte to estimate viral transmission among livestock, and spillover from livestock to humans through both direct contact and vector-mediated routes. Model simulations were used to assess the impact of vaccination on reducing the epidemic size. The rate of spillover by direct contact was about twice as high as vector transmission. Assuming 30% of the population were farmers, each transmission route contributed to 45% and 55% of the number of human infections, respectively. Reactive vaccination immunizing 20% of the livestock population reduced the number of human cases by 30%. Vaccinating 1 mo later required using 50% more vaccine doses for a similar reduction. Vaccinating only farmers required 10 times as more vaccine doses for a similar reduction in human cases. Finally, with 52.0% (95% credible interval [CrI] [42.9–59.4]) of livestock immune at the end of the epidemic wave, viral reemergence in the next rainy season (2019–2020) is unlikely. Coordinated human and animal health surveillance, and timely livestock vaccination appear to be key to controlling RVF in this setting. We furthermore demonstrate the value of a One Health quantitative approach to surveillance and control of zoonotic infectious diseases.
  • Profiling Detection and Classification of Lameness Methods in British Dairy Cattle Research: A Systematic Review and Meta-Analysis.

    Afonso, JS; Bruce, M; Keating, P; Raboisson, D; Clough, H; Oikonomou, G; Rushton, J (Frontiers Media, 2020-08-20)
    Lameness is a serious concern in the dairy sector, reflecting its high incidence and impact on animal welfare and productivity. Research has provided figures on its frequency using different methodologies, making it difficult to compare results and hindering farm-level decision-making. The study's objectives were to determine the frequency levels of lameness in British dairy cattle through a meta-analysis approach, and to understand the chronological patterns of how lameness cases are detected and classified in scientific research. A systematic review was conducted using PRISMA-P guidelines for article selection. Random-effects models estimated the pooled frequency measure of lameness with heterogeneity managed through subgroup analysis and meta-regression. Sixty-eight papers were identified, 50 included prevalence and 36 incidence data. The pooled prevalence of lameness in British dairy cattle was estimated at 29.5% (95% CI 26.7-32.4%) whilst all-cause lameness incidence rate indicated 30.9 cases of lameness per 100 cow-years (95% CI 24.5-37.9). The pooled cause-specific lameness incidence rate per 100 cow-years was 66.1 (95% CI 24.1-128.8) for white line disease, 53.2 (95% CI 20.5-101.2) for sole ulcer, 53.6 (95% CI 19.2-105.34) for digital dermatitis, with 51.9 (95% CI 9.3-129.2) attributable to other lameness-related lesions. Heterogeneity levels remained high. Sixty-nine papers contributed to a chronological overview of lameness data source. Although the AHDB Dairy mobility scoring system (MSS) was launched in the UK in 2008 and adopted shortly after by the British Dairy sector as the standard tool for assessing lameness, other methods are used depending on the investigator. Automated lameness detection systems may offer a solution for the subjective nature of MSSs, yet it was utilized in one study only. Despite the recognition of under-reporting of lameness from farm records 22 (31.9%) studies used this data source. The diversity of lameness data collection methods and sources was a key finding. It limits the understanding of lameness burden and the refinement of policy making for lameness. Standardizing case definition and research methods would improve knowledge of and ability to manage lameness. Regardless of the measurement method lameness in British dairy cattle is high.
  • Outcomes at 18 mo of 37 noma (cancrum oris) cases surgically treated at the Noma Children's Hospital, Sokoto, Nigeria.

    Farley, ES; Amirtharajah, M; Winters, RD; Taiwo, AO; Oyemakinda, MJ; Fosto, A; Torhee, LA; Mehta, UC; Bil, KA; Lenglet, AD (Oxford University Press, 2020-08-12)
    Background: Noma is a rapidly progressing infection of the oral cavity frequently resulting in severe facial disfigurement. We present a case series of noma patients surgically treated in northwest Nigeria. Methods: A retrospective analysis of routinely collected data (demographics, diagnosis and surgical procedures undergone) and in-person follow-up assessments (anthropometry, mouth opening and quality of life measurements) were conducted with patients who had surgery >6 mo prior to data collection. Results: Of the 37 patients included, 21 (56.8%) were male and 22 (62.9%) were aged >6 y. The median number of months between last surgery and follow-up was 18 (IQR 13, 25) mo. At admission, the most severely affected anatomical area was the outer cheek (n = 9; 36.0% of patients had lost between 26% and 50%). The most frequent surgical procedures were the deltopectoral flap (n = 16; 43.2%) and trismus release (n = 12; 32.4%). For the eight trismus-release patients where mouth opening was documented at admission, all had a mouth opening of 0-20 mm at follow-up. All patients reported that the surgery had improved their quality of life. Conclusions: Following their last surgical intervention, noma patients do experience some improvements in their quality of life, but debilitating long-term sequelae persist.

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