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  • Pneumococcal Meningitis Outbreaks in Africa, 2000-2018: Systematic Literature Review and Meningitis Surveillance Database Analyses.

    Franklin, K; Kwambana-Adams, B; Lessa, FC; Soeters, HM; Cooper, L; Coldiron, ME; Mwenda, J; Antonio, M; Nakamura, T; Novak, R; et al. (Oxford University Press, 2021-09-01)
    Background The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently, Streptococcus pneumoniae has been recognized as a cause of meningitis outbreaks in the region. Little is known about the natural history and epidemiology of these outbreaks, and, in contrast to meningococcal meningitis, there is no agreed definition for a pneumococcal meningitis epidemic. The aim of this analysis was to systematically review and understand pneumococcal meningitis outbreaks in Africa between 2000 and 2018. Methods Meningitis outbreaks were identified using a systematic literature review and analyses of meningitis surveillance databases. Potential outbreaks were included in the final analysis if they reported at least 10 laboratory-confirmed meningitis cases above baseline per week with ≥50% of cases confirmed as pneumococcus. Results A total of 10 potential pneumococcal meningitis outbreaks were identified in Africa between 2000 and 2018. Of these, 2 were classified as confirmed, 7 were classified as possible, and 1 was classified as unlikely. Three outbreaks spanned more than 1 year. In general, the outbreaks demonstrated lower peak attack rates than meningococcal meningitis outbreaks and had a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had higher case fatality rates than meningococcal meningitis cases. An outbreak definition, which includes a weekly district-level incidence of at least 10 suspected cases per 100 000 population per week, with >10 cumulative confirmed cases of pneumococcus per year, would have identified all 10 potential outbreaks. Conclusions Given the frequency of and high case fatality from pneumococcal meningitis outbreaks, public health recommendations on vaccination strategies and the management of outbreaks are needed. Improved laboratory testing for S. pneumoniae is critical for early outbreak identification.
  • Model of care, Noma Children's Hospital, northwest Nigeria.

    Isah, S; Amirtharajah, M; Farley, E; Semiyu Adetunji, A; Samuel, J; Oluyide, B; Bil, K; Shoaib, M; Abubakar, N; de Jong, A; et al. (Wiley Online, 2021-07-22)
    The Nigerian Ministry of Health has been offering care for noma patients for many years at the Noma Children's Hospital (NCH) in Sokoto, northwest Nigeria, and Médecins Sans Frontières has supported these initiatives since 2014. The comprehensive model of care consists of four main components: acute care, care for noma sequelae, integrated hospital-based services and community-based services. The model of care is based on the limited evidence available for prevention and treatment of noma and follows WHO's protocols for acute patients and best practice guidelines for the surgical treatment of noma survivors. The model is updated continually as new evidence becomes available, including evidence generated through the operational research studies performed at NCH. By describing the model of care, we wish to share the lessons learned with other actors working in the noma and neglected tropical disease sphere in the hope of guiding programme development.
  • Rotavirus vaccine efficacy up to 2 years of age and against diverse circulating rotavirus strains in Niger: Extended follow-up of a randomized controlled trial.

    Isanaka, S; Langendorf, C; McNeal, MM; Meyer, N; Plikaytis, B; Garba, S; Sayinzoga-Makombe, N; Soumana, I; Guindo, O; Makarimi, R; et al. (Public Library of Science, 2021-07-02)
    Background: Rotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger. Methods and findings: From August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy. Conclusions: Rotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development.
  • An intensive model of care for hepatitis C virus screening and treatment with direct-acting antivirals in people who inject drugs in Nairobi, Kenya: a model-based cost-effectiveness analysis.

    Mafirakureva, N; Stone, J; Fraser, H; Nzomukunda, Y; Maina, A; Thiong'o, AW; Kizito, KW; Mucara, EWK; Gonzalez Diaz, CI; Musyoki, H; et al. (Wiley-Blackwell, 2021-06-29)
    Background and aims: Hepatitis C virus (HCV) treatment is essential for eliminating HCV in people who inject drugs (PWID), but has limited coverage in resource-limited settings. We measured the cost-effectiveness of a pilot HCV screening and treatment intervention using directly observed therapy among PWID attending harm reduction services in Nairobi, Kenya. Design: We utilized an existing model of HIV and HCV transmission among current and former PWID in Nairobi to estimate the cost-effectiveness of screening and treatment for HCV, including prevention benefits versus no screening and treatment. The cure rate of treatment and costs for screening and treatment were estimated from intervention data, while other model parameters were derived from literature. Cost-effectiveness was evaluated over a life-time horizon from the health-care provider's perspective. One-way and probabilistic sensitivity analyses were performed. Setting: Nairobi, Kenya. Population: PWID. Measurements: Treatment costs, incremental cost-effectiveness ratio (cost per disability-adjusted life year averted). Findings: The cost per disability-adjusted life-year averted for the intervention was $975, with 92.1% of the probabilistic sensitivity analyses simulations falling below the per capita gross domestic product for Kenya ($1509; commonly used as a suitable threshold for determining whether an intervention is cost-effective). However, the intervention was not cost-effective at the opportunity cost-based cost-effectiveness threshold of $647 per disability-adjusted life-year averted. Sensitivity analyses showed that the intervention could provide more value for money by including modelled estimates for HCV disease care costs, assuming lower drug prices ($75 instead of $728 per course) and excluding directly-observed therapy costs. Conclusions: The current strategy of screening and treatment for hepatitis C virus (HCV) among people who inject drugs in Nairobi is likely to be highly cost-effective with currently available cheaper drug prices, if directly-observed therapy is not used and HCV disease care costs are accounted for.
  • No Evidence Known Viruses Play a Role in the Pathogenesis of Onchocerciasis-Associated Epilepsy. An Explorative Metagenomic Case-Control Study.

    Roach, M; Cantu, A; Vieri, MK; Cotten, M; Kellam, P; Phan, M; Hoek, LV; Mandro, M; Tepage, F; Mambandu, G; et al. (MDPI, 2021-06-22)
    Despite the increasing epidemiological evidence that the Onchocerca volvulus parasite is strongly associated with epilepsy in children, hence the name onchocerciasis-associated epilepsy (OAE), the pathophysiological mechanism of OAE remains to be elucidated. In June 2014, children with unprovoked convulsive epilepsy and healthy controls were enrolled in a case control study in Titule, Bas-Uélé Province in the Democratic Republic of the Congo (DRC) to identify risk factors for epilepsy. Using a subset of samples collected from individuals enrolled in this study (16 persons with OAE and 9 controls) plasma, buffy coat, and cerebrospinal fluid (CSF) were subjected to random-primed next-generation sequencing. The resulting sequences were analyzed using sensitive computational methods to identify viral DNA and RNA sequences. Anneloviridae, Flaviviridae, Hepadnaviridae (Hepatitis B virus), Herpesviridae, Papillomaviridae, Polyomaviridae (Human polyomavirus), and Virgaviridae were identified in cases and in controls. Not unexpectedly, a variety of bacteriophages were also detected in all cases and controls. However, none of the identified viral sequences were found enriched in OAE cases, which was our criteria for agents that might play a role in the etiology or pathogenesis of OAE.
  • High burden of cryptococcal antigenemia and meningitis among patients presenting at an emergency department in Maputo, Mozambique.

    Deiss, R; Loerti, CV; Gutierrez, AG; Filipe, E; Tatia, M; Issufo, S; Ciglenecki, I; Loarec, A; Vivaldo, H; Barra, C; et al. (Public Library of Science, 2021-04-26)
    Background: Cryptococcal meningitis is a leading cause of HIV-related mortality in sub-Saharan Africa, however, screening for cryptococcal antigenemia has not been universally implemented. As a result, data concerning cryptococcal meningitis and antigenemia are sparse, and in Mozambique, the prevalence of both are unknown. Methods: We performed a retrospective analysis of routinely collected data from a point-of-care cryptococcal antigen screening program at a public hospital in Maputo, Mozambique. HIV-positive patients admitted to the emergency department underwent CD4 count testing; those with pre-defined abnormal vital signs or CD4 count ≤ 200 cells/μL received cryptococcal antigen testing and lumbar punctures if indicated. Patients with CM were admitted to the hospital and treated with liposomal amphotericin B and flucytosine; their 12-week outcomes were ascertained through review of medical records or telephone contact by program staff made in the routine course of service delivery. Results: Among 1,795 patients screened for cryptococcal antigenemia between March 2018-March 2019, 134 (7.5%) were positive. Of patients with cryptococcal antigenemia, 96 (71.6%) were diagnosed with CM, representing 5.4% of all screened patients. Treatment outcomes were available for 87 CM patients: 24 patients (27.6%) died during induction treatment and 63 (72.4%) survived until discharge; of these, 38 (60.3%) remained in care, 9 (14.3%) died, and 16 (25.3%) were lost-to follow-up at 12 weeks. Conclusions: We found a high prevalence of cryptococcal antigenemia and meningitis among patients screened at an emergency department in Maputo, Mozambique. High mortality during and after induction therapy demonstrate missed opportunities for earlier detection of cryptococcal antigenemia, even as point-of-care screening and rapid assessment in an emergency room offer potential to improve outcomes.
  • 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.
  • hlers

    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.

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