Clinical manifestations of human brucellosis : a systematic review and meta-analysis

BACKGROUND: The objectives of this systematic review, commissioned by WHO, were to assess the frequency and severity of clinical manifestations of human brucellosis, in view of specifying a disability weight for a DALY calculation. METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, with 2,385 articles published between January 1990-June 2010 identified as relating to human brucellosis. Fifty-seven studies were of sufficient quality for data extraction. Pooled proportions of cases with specific clinical manifestations were stratified by age category and sex and analysed using generalized linear mixed models. Data relating to duration of illness and risk factors were also extracted. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from epididymo-orchitis. Debilitating conditions such as arthralgia, myalgia and back pain affected around half of the patients (65%, 47% and 45%, respectively). Given that 78% patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas. Significant delays in appropriate diagnosis and treatment were the result of health service inadequacies and socioeconomic factors. Based on disability weights from the 2004 Global Burden of Disease Study, a disability weight of 0.150 is proposed as the first informed estimate for chronic, localised brucellosis and 0.190 for acute brucellosis. CONCLUSIONS: This systematic review adds to the understanding of the global burden of brucellosis, one of the most common zoonoses worldwide. The severe, debilitating, and chronic impact of brucellosis is highlighted. Well designed epidemiological studies from regions lacking in data would allow a more complete understanding of the clinical manifestations of disease and exposure risks, and provide further evidence for policy-makers. As this is the first informed estimate of a disability weight for brucellosis, there need for further debate amongst brucellosis experts and a consensus to be reache

Novel tools and strategies for breaking schistosomiasis transmission: study protocol for an intervention study

BACKGROUND: Global elimination of schistosomiasis as a public health problem is set as target in the new World Health Organization's Neglected Tropical Diseases Roadmap for 2030. Due to a long history of interventions, the Zanzibar islands of Tanzania have reached this goal since 2017. However, challenges occur on the last mile towards interruption of transmission. Our study will investigate new tools and strategies for breaking schistosomiasis transmission. METHODS: The study is designed as an intervention study, documented through repeated cross-sectional surveys (2020-2024). The primary endpoint will be the sensitivity of a surveillance-response approach to detect and react to outbreaks of urogenital schistosomiasis over three years of implementation. The surveys and multi-disciplinary interventions will be implemented in 20 communities in the north of Pemba island. In low-prevalence areas, surveillance-response will consist of active, passive and reactive case detection, treatment of positive individuals, and focal snail control. In hotspot areas, mass drug administration, snail control and behaviour change interventions will be implemented. Parasitological cross-sectional surveys in 20 communities and their main primary schools will serve to adapt the intervention approach annually and to monitor the performance of the surveillance-response approach and impact of interventions. Schistosoma haematobium infections will be diagnosed using reagent strips and urine filtration microscopy, and by exploring novel point-of-care diagnostic tests. DISCUSSION: Our study will shed light on the field applicability and performance of novel adaptive intervention strategies, and standard and new diagnostic tools for schistosomiasis elimination. The evidence and experiences generated by micro-mapping of S. haematobium infections at community level, micro-targeting of new adaptive intervention approaches, and application of novel diagnostic tools can guide future strategic plans for schistosomiasis elimination in Zanzibar and inform other countries aiming for interruption of transmission. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493

Efficacy, safety and acceptability of a new chewable formulationversusthe solid tablet of mebendazole against hookworm infections in children: an open-label, randomized controlled trial

Background; : Soil-transmitted helminths (STHs) infect almost 1·5 billion people worldwide. The control of STH infections is based on preventive chemotherapy using either albendazole or mebendazole. Before being widely used, a sufficient body of evidence on efficacy, safety and acceptability is warranted for the new chewable child-friendly formulation of mebendazole that was recently developed.; Methods; : We conducted a randomised controlled superiority trial in four primary schools and kindergartens on Pemba Island, Tanzania. We considered eligible children aged 3 to 12 years with a hookworm infection intensity of at least 50 eggs per gram (EPG) of stool and no chronic diseases. Participants were allocated to treatment arms (ratio 1:1) using a computer generated random sequence. Our primary outcome was geometric mean based egg reduction rate (ERR) against hookworm assessed 14-21 days post-treatment. This trial complete and is registered with ClinicalTrials.gov, number NCT03995680 (June 24, 2019).; Findings; : 397 children were eligible and randomised into the solid (198) or chewable (199) tablet arms, of whom 393 were analysed. We found no significant difference between both formulations in terms of ERR (solid 70·8% versus chewable 68·5%, difference in ERRgeometric mean 2·3%-points, 95% CI -7·8 to 12·6, p = 0.65) and CR (11·2 versus 12·7%, 95% CI -4·9 to 7·9, p = 0.65) against hookworm infections. Adverse events were mild in both treatment arms.; Interpretations; : Though we could not demonstrate superiority in terms of efficacy of the new formulation, the difference between arms was small and therefore, the chewable formulation could be safely used as an alternative to swallowable tablets, in particular in young children who may have swallowing difficulties. This might help increase compliance and, consequently, enhance the effect of preventive chemotherapy

Effectiveness of a home-environmental intervention package and an early child development intervention on child health and development in high-altitude rural communities in the Peruvian Andes: a cluster-randomised controlled trial

Unsafe drinking water, poor sanitation and hygiene, exposure to household air pollution and low cognitive and socio-emotional stimulation are risk factors affecting children in low- and middle-income countries. We implemented an integrated home-environmental intervention package (IHIP), comprising a kitchen sink, hygiene education and a certified improved biomass cookstove, and an early child development (ECD) programme to improve children´s health and developmental outcomes in the rural high-altitude Andes of Peru

GPS-based fine-scale mapping surveys for schistosomiasis assessment: a practical introduction and documentation of field implementation

BACKGROUND: Fine-scale mapping of schistosomiasis to guide micro-targeting of interventions will gain importance in elimination settings, where the heterogeneity of transmission is often pronounced. Novel mobile applications offer new opportunities for disease mapping. We provide a practical introduction and documentation of the strengths and shortcomings of GPS-based household identification and participant recruitment using tablet-based applications for fine-scale schistosomiasis mapping at sub-district level in a remote area in Pemba, Tanzania. METHODS: A community-based household survey for urogenital schistosomiasis assessment was conducted from November 2020 until February 2021 in 20 small administrative areas in Pemba. For the survey, 1400 housing structures were prospectively and randomly selected from shapefile data. To identify pre-selected structures and collect survey-related data, field enumerators searched for the houses' geolocation using the mobile applications Open Data Kit (ODK) and MAPS.ME. The number of inhabited and uninhabited structures, the median distance between the pre-selected and recorded locations, and the dropout rates due to non-participation or non-submission of urine samples of sufficient volume for schistosomiasis testing was assessed. RESULTS: Among the 1400 randomly selected housing structures, 1396 (99.7%) were identified by the enumerators. The median distance between the pre-selected and recorded structures was 5.4 m. A total of 1098 (78.7%) were residential houses. Among them, 99 (9.0%) were dropped due to continuous absence of residents and 40 (3.6%) households refused to participate. In 797 (83.1%) among the 959 participating households, all eligible household members or all but one provided a urine sample of sufficient volume. CONCLUSIONS: The fine-scale mapping approach using a combination of ODK and an offline navigation application installed on tablet computers allows a very precise identification of housing structures. Dropouts due to non-residential housing structures, absence, non-participation and lack of urine need to be considered in survey designs. Our findings can guide the planning and implementation of future household-based mapping or longitudinal surveys and thus support micro-targeting and follow-up of interventions for schistosomiasis control and elimination in remote areas. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493

Integrated community based human and animal syndromic surveillance in Adadle district of the Somali region of Ethiopia

The economy of Ethiopia largely depends on agriculture and roughly 80% of the households have direct contact with domestic animals which make the community vulnerable to zoonotic diseases, especially in pastoral areas like the Somali Regional State (SRS) of Ethiopia. However, in addition to low reporting rates, especially in livestock, there is also lack of coordination between public health and animal health surveillance and there is no linkage between public health system and animal health system and mechanism or structure for sharing information on zoonotic diseases in SRS. In view of these challenges, a small scale study was conducted to evaluate the feasibility of mobile communication in the early detection of human and animal syndromes in remote pastoral areas including where there are no human and animal health facilities by engaging local communities in the diseases surveillance. Method: A small scale study, testing a community based human and animal syndromic surveillance was conducted from August 2017 to February 2018 in 20 villages in four Kebeles of Adadle district in the SRS with an estimated 1390 households and 112,850 livestock. The selected community leaders were trained on disease surveillance and detection. The communication was done by direct calls. Two dollars per month were provided to the village leaders recruited for the surveillance. Results: A total of 904 and 671 human and animal syndrome cases were reported in seven months of the study period. In addition to syndromes, suspected anthrax, sheep and goat pox (SGP), rabies, salmonellosis and mass abortion outbreaks were reported in animals. In humans, suspected cholera and chicken pox outbreaks were reported. Furthermore, tuberculosis and malaria cases were also confirmed in the study villages. In humans, gastrointestinal tract (GIT) disorder was the most common syndrome observed, which constituted (42.8%) of all syndromes, followed by respiratory disorder (37.8%) and febrile illness (15.5%). In livestock, cattle contributed (40.8%) of all cases of illness, while sheep, goats and camels contributed 24.1%, 18% and 17% of the cases respectively. Responses were organized for emergency treatment and vaccination campaigns against certain suspected disease outbreaks and emergencies such as SGP and cholera. Conclusion: This study suggests that engaging and empowering the village local leaders in disease surveillance in pastoral setting areas, including where there are no human and animal health facilities, coupled with mobile technologies (non-smart phone), would improve early detection and response to human and animal health events including zoonotic emergencies, and consequently improve the reporting rate at district, regional and national level. However, the collaboration between sectors (human health and animals health) and the capacity to respond to zoonotic diseases and etiological identification are crucial elements for effective integrated human and animals disease surveillance and response

Long-term outcomes of ivermectin-albendazole versus albendazole alone against soil-transmitted helminths: results from randomized controlled trials in Lao PDR and Pemba Island, Tanzania

BACKGROUND: Preventive chemotherapy is the cornerstone of soil-transmitted helminth (STH) control. Long-term outcomes and adequate treatment frequency of the recently recommended albendazole-ivermectin have not been studied to date. METHODOLOGY/PRINCIPAL FINDINGS: Double-blind randomized controlled trials were conducted in Lao PDR, Pemba Island, Tanzania and Cote d'Ivoire between 2018 and 2020 to evaluate the efficacy and safety of ivermectin-albendazole versus albendazole-placebo in Trichuris trichiura-infected individuals aged 6 to 60. In the framework of this study, in Lao PDR 466 and 413 participants and on Pemba Island, 558 and 515 participants were followed-up six and 12 months post-treatment, respectively. From each participant at least one stool sample was processed for Kato-Katz diagnosis and cure rates (CRs), egg reduction rates (ERRs) and apparent reinfection rates were calculated. If found helminth-positive at 6-months, participants were re-treated according to their allocated treatment. Long-term outcomes against T. trichiura based on CRs and ERRs of ivermectin-albendazole compared to albendazole were significantly higher at six months in Lao PDR (CR, 65.8% vs 13.4%, difference; 52.4; 95% CI 45.0-60.0; ERRs: 99.0% vs 79.6, difference 19.4; 95% CI 14.4-24.4) and Pemba Island (CR: 17.8 vs 1.4%, difference; 16.4%; 95% CI 11.6-21.0; ERRs: 84.9 vs 21.2, difference 63.8; 95% CI 50.6-76.9) and also at 12 months in Lao PDR (CR, 74.0 vs 23.4%, difference; 50.6; 95% CI 42.6-61.0; ERRs: 99.6 vs 91.3, difference 8.3; 95% CI 5.7-10.8) and Pemba Island (CR, 19.5 vs 3.4%, difference; 16.1; 95% CI 10.7-21.5; ERRs: 92.9 vs 53.6, difference 39.3; 95% CI 31.2-47.4) respectively. Apparent reinfection rates with T. trichiura were considerably higher on Pemba Island (100.0%, 95% CI, 29.2-100.0) than in Lao PDR (10.0%, 95% CI, 0.2-44.5) at 12 months post-treatment for participants treated with albendazole alone. CONCLUSIONS/SIGNIFICANCE: The long-term outcomes against T. trichiura of ivermectin-albendazole are superior to albendazole in terms of CRs and ERRs and in reducing infection intensities. Our results will help to guide decisions on how to best use ivermectin-albendazole in the context of large-scale PC programs tailored to the local context to sustainably control STH infections. TRIAL REGISTRATION: ClinicalTrials.gov registered with clinicaltrials.gov, reference: NCT03527732, date assigned: 17 May 2018

Efficacy and safety of moxidectin and albendazole compared to ivermectin and albendazole co-administration in adolescents infected with Trichuris trichiura: a randomized controlled trial protocol

Background: Infections with soil-transmitted helminths (STHs) predominantly affect impoverished populations in tropical environments. The periodic administration of single dose benzimidazoles (i.e., albendazole, mebendazole) to at-risk individuals in endemic regions is at the center of STH control strategies. Given the low efficacy of these drugs against trichuriasis, investigation of drug combinations including moxidectin and ivermectin has recently been initiated, yet the identification of the best treatment option requires more research. We present the protocol for a trial investigating the efficacy and safety of co-administered moxidectin and albendazole compared to co-administered ivermectin and albendazole against Trichuris trichiura. Methods: We will conduct a randomized controlled trial enrolling 540 T. trichiura-infected adolescents aged 12-19 years on Pemba Island (Tanzania). The trial will be open-label with blinded outcome assessors. The primary objective is to demonstrate non-inferiority of orally co-administered single-dose moxidectin (8 mg)/albendazole (400 mg) compared to orally co-administered single-dose ivermectin (200 microg/kg)/albendazole (400 mg) in terms of egg reduction rates (ERRs) against T. trichiura infections assessed by Kato-Katz at 14-21 days post-treatment. Secondary objectives include the assessment of the drug combinations' superiority compared to their respective monotherapies, of the cure rates (CRs) against T. trichiura, and the safety and tolerability of all treatments, as well as CRs and ERRs against concomitant STH infections ( Ascaris lumbricoides and hookworm). Potential effects of the treatment regimens on follow-up prevalences of STH at 5-6 weeks and 3 months post-treatment and pharmacokinetic/ pharmacodynamic parameters will also be assessed. Conclusions: Results from this trial will help to inform decision- and policymakers on which anthelminthic combination therapy might improve existing deworming programs and provide a valuable adjunct tool for interrupting STH transmission. Clinicaltrials.gov registration: NCT04700423 (07/01/2021)

Fine-scale-mapping of Schistosoma haematobium infections at the school and community levels and intermediate host snail abundance in the north of Pemba Island: baseline cross-sectional survey findings before the onset of a 3-year intervention study

BACKGROUND: Schistosomiasis elimination has gained renewed priority in the WHO guidance documents published in 2020 and 2022. The SchistoBreak project, implemented in Pemba, Tanzania between 2020 and 2024, aims to assess new tools and strategies for shifting from elimination as a public health problem towards interruption of transmission. Here we report our baseline findings and discuss implications for future interventions. METHODS: In 2020, human water contact sites (HWCSs) in the study area were geolocated and snail surveys were conducted. A parasitological and questionnaire cross-sectional baseline survey was implemented in 20 communities and their 16 primary schools between November 2020 and February 2021. Urine samples were collected at the school and household levels from individuals aged >/= 4 years. Schistosoma haematobium infection was detected by urine filtration microscopy. Snail, parasitological and questionnaire-derived data were analyzed descriptively, spatially and with generalized estimated equation models. RESULTS: The intermediate host snail Bulinus globosus was detected in 19.8% (33/167) of HWCSs. The overall S. haematobium prevalence was 1.2% (26/2196) in school-aged children and 0.8% (31/3893) in community members, with 0.2% (4/2196) and 0.1% (3/3893) heavy-intensity infections, respectively. Children who studied 2 km away (odds ratio [OR]: 5.0; 95% confidence interval [CI]: 2.3-11.1). Individuals living in a house located 2 km distance (OR: 18.0; 95% CI: 2.9-111.0). Self-reported praziquantel treatment coverage was 83.2% (2015/2423) in schoolchildren in the mass drug administration (MDA) conducted in August 2020. Coverage among adult community members was 59.9% (574/958), but only 34.8% (333/958) took praziquantel correctly. CONCLUSIONS: While the S. haematobium prevalence is very low in Pemba, there are many HWCSs with B. globosus situated close to schools or houses that pose a considerable risk of recrudescence. To maintain and accelerate the progress towards interruption of transmission, targeted and cost-effective interventions that are accepted by the community are needed; for example, snail control plus focal MDA, or test-and-treat in schools and households near infested waterbodies

Household-level risk factors for water contamination and antimicrobial resistance in drinking water among households with children under 5 in rural San Marcos, Cajamarca, Peru

Household water contamination at point of use depends on human, animal and environmental factors embodying all aspects of a One Health approach. This study investigated the association between household factors, the presence of thermotolerant coliform, and the presence of antibiotic resistant bacteria in drinking water among 314 households with children under 5 in Cajamarca, Peru. This study analysed data from a baseline sampling of a randomized controlled trial, including household surveys covering household water management and factors such as household animals, as well as microbiological data from samples collected from drinking water. Data were analysed using generalized linear models. Drinking water samples collected from narrow-mouthed containers were less likely to be contaminated than samples collected from the faucet (OR = 0.55, p = 0.030) or wide mouthed containers. The presence of thermotolerant coliform was associated with owning farm birds, which increased the proportion of contamination from 42.2% to 59.1% (OR = 1.98, p = 0.017) and with animal waste observed in the kitchen area, which increased the prevalence of contamination from 51.4% to 65.6% (OR = 1.80, p = 0.024). Resistance to any antibiotic was higher among pig owners at 60%, relative to non-pig owners at 36.4% (OR = 1.97, p = 0.012) as well as households with free-roaming animals in the kitchen area at 59.6% compared to households without free-roaming animals at 39.7% (OR = 2.24, p = 0.035). Recent child antibiotic use increased the prevalence of trimethoprim-sulfamethoxazole resistance among E. coli isolates to 22.3% relative to 16.7% (OR = 3.00, p = 0.037). Overall, these findings suggest that water storage in a secure container to protect from in-home contamination is likely to be important in providing safe drinking water at point of use. In addition, transmission of thermotolerant coliform and AMR between domestic animals and human drinking water supplies is likely. Further research should explore transmission pathways and methods to support safe drinking water access in multi-species households