Posttraumatic stress disorder and psycho-social impairment following snakebite in Northeastern Nigeria.

BACKGROUND: Snakebite is a major public health problem among impoverished rural populations causing considerable morbidity and mortality in West Africa. Despite the huge burden of snakebite in this region, psycho-social impairment following snakebite has not been evaluated. In this study, we assessed for features of posttraumatic stress disorder and psycho-social impairment among rural snakebite victims in Northeastern Nigeria. METHODS: Individuals with previous snakebite managed in our facility, defined as exposed to snakebite, and their matched relatives not exposed to snakebite were invited to participate in the study following community mobilization. A retrospective cohort study was conducted evaluating the presence of psycho-social functioning, posttraumatic stress disorder, quality of life, social disability, cognitive impairment, and psychological morbidity using standard tools administered by the investigators, trained nurses, and community health workers. RESULTS: The prevalence of features of posttraumatic stress disorder among those exposed to snakebite compared to those not exposed to snakebite was 43% and 28%, respectively (risk ratio = 1.53; 95% confidence interval: 1.04-2.24; p = 0.024). Subjects exposed to snakebite had significantly poorer quality of life score in the psychological and social domains (p < 0.05). Other psycho-social complications associated with snakebite were impaired family/school functioning and psychological morbidity. No difference in cognitive functioning was observed between the two groups. CONCLUSIONS: Snakebite is complicated by features of posttraumatic stress disorder, poor quality of life, and psycho-social impairments in northeastern Nigeria. Detection, monitoring, and appropriate management interventions should be provided and made more accessible to snakebite victims to ameliorate mental and psychological impairment.

Cost-optimization in the treatment of multidrug resistant tuberculosis in Nigeria.

OBJECTIVE: To compare the cost of facility-based MDR TB care (F) to home-based care (H) from the perspective of the Nigerian national health system. METHODS: We assessed the expected costs of the two MDR TB treatment approaches using a decision-analytic model with a follow-up of 6 months. MDR TB treatment outcomes were obtained from a systematic review of randomised clinical trials. The outcomes of interest included treatment success, treatment failure, treatment default and mortality and did not vary significantly between the two alternatives. Treatment costs included the cost of the following: drug therapy (F, H), hospital stay (F), nurse care (F, H), physician care (F), nursing facility (F) and transport to the healthcare provider (H). Finally, we estimated the potential cost savings associated with home-based treatment for all patients starting MDR TB treatment in Nigeria. RESULTS: The average expected total treatment cost for a Nigerian patient treated for MDR TB was estimated at US2095 for facility - based care and 1535 for home-based care, a potential saving of 25%. One of the major drivers of this difference is significantly more intensive, and therefore more costly, nursing care in hospitals. In 2013, a total of 426 patients were initiated on facility-based MDR TB treatment in Nigeria. Thus, the potential savings through home-based care are US$ 223 204 per year. CONCLUSION: In Nigeria, treatment of MDR TB using home-based care is expected to result in similar patient outcomes at markedly reduced public health costs as facility-based care.

Newborn screening and prophylactic interventions for sickle cell disease in 47 countries in sub-Saharan Africa: a cost-effectiveness analysis.

BACKGROUND: Sickle cell disease (SCD) constitutes a major public health problem in sub-Saharan Africa (SSA). Newborn screening and early subsequent clinical intervention can reduce early mortality and increase life expectancy, but have not been widely implemented in SSA. This analysis assesses the cost-effectiveness of a newborn screening and prophylactic intervention (NSPI) package for SCD in 47 SSA countries. METHODS: A lifetime Markov model with annual cycles was built with infants either being screened using isoelectric focusing (IEF) or not screened. Confirmed positive cases received interventions including insecticide-treated mosquito bed nets, folic acid supplementation, prophylactic antimalarial and penicillin therapy, and vaccinations against bacterial infections. Estimates for the local incidence of SCD, the life expectancy of untreated children, the SCD disability weight, and the cost of screening laboratory tests were based on published sources. Among treated infants, the annual probability of mortality until 30 years of age was derived from a pediatric hospital-based cohort. The outcome of interest included a country-specific cost per Disability Adjusted Life Year (DALY) averted. RESULTS: Of 47 modeled countries in SSA, NSPI is almost certainly highly cost-effective in 24 countries (average cost per DALY averted: US$184); in 10 countries, it is cost-effective in the base case (average cost per DALY averted: US$285), but the results are subject to uncertainty; in the remaining 13, it is most likely not cost-effective. We observe a strong inverse relationship between the incidence rate of SCD and the cost per DALY averted. Newborn screening is estimated to be cost-effective as long as the incidence rate exceeds 0.2-0.3 %, although in some countries NSPI is cost-effective at incidence rates below this range. In total, NSPI could avert over 2.4 million disability adjusted life years (DALYs) annually across SSA. CONCLUSIONS: Using IEF to screen all newborns for SCD plus administration of prophylactic interventions to affected children is cost-effective in the majority of countries in SSA.

Estimating the Public Health Burden Associated With Adverse Pregnancy Outcomes Resulting From Syphilis Infection Across 43 Countries in Sub-Saharan Africa.

BACKGROUND: Untreated syphilis in pregnancy is associated with adverse clinical outcomes to the infant. The study aimed to estimate the public health burden resulting from adverse pregnancy outcomes due to syphilis infection among pregnant women not screened for syphilis in 43 countries in sub-Saharan Africa. METHODS: Estimated country-specific incidence of syphilis was generated from annual number of live births, the proportion of women with at least 1 antenatal care (ANC) visit, the syphilis prevalence rate, and the proportion of women screened for syphilis during ANC.Adverse pregnancy outcome data (stillbirth, neonatal death, low birth weight, and congenital syphilis) were obtained from published sources. Disability-adjusted life-year (DALY) estimates were calculated using undiscounted local life expectancy, the neonatal standard loss function, and relevant disability weights. The model assessed the potential impact of raising ANC coverage to at least 95% and syphilis screening to at least 95% (World Health Organization targets). RESULTS: For all 43 sub-Saharan Africa countries, the estimated incidence of adverse pregnancy outcomes was 205,901 (95% confidence interval [CI], 113,256-383,051) per year, including stillbirth (88,376 [95% CI, 60,854-121,713]), neonatal death (34,959 [95% CI, 23,330-50,076]), low birth weight (22,483 [95% CI, 0-98,847]), and congenital syphilis (60,084 [95% CI, 29,073-112,414]), resulting in approximately 12.5 million DALYs. Countries with the greatest burden are (in DALYs, millions) Democratic Republic of the Congo (1.809), Nigeria (1.598), Ethiopia (1.466), and Tanzania (0.961). Attaining World Health Organization targets could reduce the burden by 8.5 million DALYs. CONCLUSIONS: Substantial infant mortality and morbidity results from maternal syphilis infection concentrated in countries with low access to ANC or low rates of syphilis screening.

Effect of distance and delay in access to care on outcome of snakebite in rural north-eastern Nigeria.

INTRODUCTION: Snakebite envenoming is a major cause of morbidity and mortality in rural areas of the tropics. Timely administration of effective antivenom remains the mainstay of management. METHODS: The study was a quantitative descriptive study aimed at exploring the causes and effects of delay, distance and time taken to access care on snakebite outcomes in Nigeria. All prospective snakebite victims reporting to Kaltungo General Hospital were enrolled. Data on demography, date and time bitten, date and time admitted, site of bite, circumstances of snakebite, responsible snake, clinical features, 20-minute whole-blood clotting test, antivenom administered and outcome were recorded. Delay arising from use of traditional first aid (TFA), time elapsed from snakebite to presentation and the shortest distance from bite location to the hospital was calculated or obtained using a global positioning system. RESULTS: The association between delay before hospital presentation and poor outcome was not statistically significant, even though there was a 2% higher likelihood of poor outcome among those with a 1-hour delay compared to those without delay (odds ratio 1.02, 95% confidence interval 1.00-1.03). There was no difference in distance from bite location to hospital between those with a poor outcome (74) compared to those with a good outcome (325). Those with a poor outcome had more severe envenomation requiring more antivenoms and longer hospital stays. Given poor access to antivenom therapy at distant locations ≥100 km, victims were more likely to use TFA such as black 'snake' stone, with consequent prolonged delays. Antivenoms should be more readily available at distant places. CONCLUSIONS: Community education on avoiding potentially harmful TFA and prompt access to care is recommended. There is a need to provide snakebite care to multiple peripheral, relatively more rural inaccessible areas.

Hospitalization and mortality outcomes among adult persons living with HIV in a tertiary hospital in South-western Nigeria: A cross-sectional study.

HIV infection continues to be a major public health issue, with significant morbidity and mortality especially in resource poor areas. Infection with HIV results in an increased risk of opportunistic infections and other complications, which may lead to hospital admission and death. Morbidity and mortality patterns among hospitalized persons living with HIV (PLHIV) have been well documented in high income countries, but there is paucity of such data in Nigeria. We investigated the reasons for hospitalization and predictors of death among adult PLHIV at the Federal Medical Center (FMC) Abeokuta, Nigeria. This was a hospital based cross-sectional study carried out over a 15-month period between January 2018 and March 2019. All consenting hospitalized adult PLHIV who met the inclusion criteria were enrolled into the study. Causes of hospitalization and death were obtained and analyzed. Over the study period, 193 hospitalizations of PLHIV were studied. Although a number of clinical syndromes were documented, Sepsis and Tuberculosis were the commonest causes of hospitalization and mortality. Mortality rate was 37(19.2%) for outcomes on day 30, with anaemia [OR 3.00 (95% C.I: 1.04-8.67)], poor adherence with Cotrimoxazole [OR 4.07 (95% C.I: 1.79-9.28)], poor adherence with cART [OR 13.40 (95% C.I: 3.92-45.44)], and a longer duration of fever [OR 3.34 (95% C.I: 1.10-9.99)] being predictors of mortality. Part of the study's limitation was resource-constraint of some of the indigent patient which affected their ability to access some diagnostic investigations and get optimal care thereby impacting on their outcome. Despite the upscaling of cART, opportunistic infections and sepsis remain common causes of hospitalization and death in adult PLHIV. More attention should therefore be placed on early diagnosis, prevention of immunosuppression and sepsis through timely administration and adherence to cART and other prophylactic measures.

Landscape of toxin-neutralizing therapeutics for snakebite envenoming (2015-2022): Setting the stage for an R&D agenda.

BACKGROUND: Progress in snakebite envenoming (SBE) therapeutics has suffered from a critical lack of data on the research and development (R&D) landscape. A database characterising this information would be a powerful tool for coordinating and accelerating SBE R&D. To address this need, we aimed to identify and categorise all active investigational candidates in development for SBE and all available or marketed products. METHODOLOGY/PRINCIPAL FINDINGS: In this landscape study, publicly available data and literature were reviewed to canvas the state of the SBE therapeutics market and research pipeline by identifying, characterising, and validating all investigational drug and biologic candidates with direct action on snake venom toxins, and all products available or marketed from 2015 to 2022. We identified 127 marketed products and 196 candidates in the pipeline, describing a very homogenous market of similar but geographically bespoke products and a diverse but immature pipeline, as most investigational candidates are at an early stage of development, with only eight candidates in clinical development. CONCLUSIONS/SIGNIFICANCE: Further investment and research is needed to address the shortfalls in products already on the market and to accelerate R&D for new therapeutics. This should be accompanied by efforts to converge on shared priorities and reshape the current SBE R&D ecosystem to ensure translation of innovation and access.

Noma disease among internally displaced persons in Northeast Nigeria: a retrospective descriptive study.

Background: Recently recognized by the World Health Organization as a neglected tropical disease, Noma, an acute and destructive gangrenous disease affecting the gums and facial structures within the oral cavity, has a high mortality rate if untreated. Objectives: To investigate the prevalence and impact of Noma among internally displaced populations in Northeastern Nigeria. Design: A retrospective study. Methods: This retrospective study investigates the prevalence and impact of Noma among internally displaced populations in Northeastern Nigeria. Noma is endemic in Northern Nigeria, Africa, and its occurrence has been linked to extreme poverty, malnutrition, poor hygiene, and inadequate healthcare - conditions exacerbated by the ongoing Boko Haram conflict. Results: The retrospective descriptive cross-sectional analysis of 17 cases reveals a median age of 8 years, with most of the patients being children who suffer significant social stigmas, such as difficulties in speaking, eating, and social integration, including reduced school attendance and marital prospects. Conclusion: The study highlights the urgent need for comprehensive research into the etiology of Noma and its socio-economic impact. It emphasizes the necessity for early and effective intervention strategies, particularly in conflict-stricken areas with limited healthcare access.

Investigating Snake-Venom-Induced Dermonecrosis and Inflammation Using an Ex Vivo Human Skin Model.

Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the first time, an ex vivo, non-perfused human skin model was used to investigate temporal histopathological and immunological changes following subcutaneous injections of venoms from medically important African vipers (Echis ocellatus and Bitis arietans) and cobras (Naja nigricollis and N. haje). Histological analysis of venom-injected ex vivo human skin biopsies revealed morphological changes in the epidermis (ballooning degeneration, erosion, and ulceration) comparable to clinical signs of local envenoming. Immunostaining of these biopsies confirmed cell apoptosis consistent with the onset of necrosis. RNA sequencing, multiplex bead arrays, and ELISAs demonstrated that venom-injected human skin biopsies exhibited higher rates of transcription and expression of chemokines (CXCL5, MIP1-ALPHA, RANTES, MCP-1, and MIG), cytokines (IL-1ß, IL-1RA, G-CSF/CSF-3, and GM-CSF), and growth factors (VEGF-A, FGF, and HGF) in comparison to non-injected biopsies. To investigate the efficacy of antivenom, SAIMR Echis monovalent or SAIMR polyvalent antivenom was injected one hour following E. ocellatus or N. nigricollis venom treatment, respectively, and although antivenom did not prevent venom-induced dermal tissue damage, it did reduce all pro-inflammatory chemokines, cytokines, and growth factors to normal levels after 48 h. This ex vivo skin model could be useful for studies evaluating the progression of local envenoming and the efficacy of snakebite treatments.

Challenges and prospects of managing non-acute medical conditions among pastoral populations in sub-Saharan Africa.

In Africa, pastoral populations face several underrecognized health issues. The livelihoods of pastoralists revolve around possession of livestock and they are constantly moving in search of water and pasturage. They are predisposed to chronic zoonotic infections but may also suffer from non-acute non-zoonotic cosmopolitan infectious and non-infectious chronic medical conditions. Given their migratory lifestyle, livelihood, geographic inaccessibility, communication barriers, illiteracy and poverty, it is challenging for pastoralists to access lengthy inpatient clinical care and long-term periodic follow-up that may be required to achieve control or cure of subacute, chronic or lifelong diseases. The challenges and management modalities of complicated subacute bacterial endocarditis requiring critical clinical considerations, long-term medical and surgical interventions in a stateless Arab camel herder are described to highlight the plight of pastoralists. Innovative clinical and public health strategies are suggested to authorities and healthcare institutions to improve access to care for non-acute diseases among them.

Lifetime prevalence and knowledge of snakebite among graduates in Nigeria.

BACKGROUND: Given the lack of studies on snakebite envenoming knowledge in the general population, we examined the lifetime prevalence of snakebite and knowledge of snakebite and its prevention and first aid among recent Nigerian graduates in national service. METHODS: This questionnaire-based cross-sectional study involved 351 consenting national youth corps members at a rural orientation camp in Kano, Nigeria. RESULTS: Participants' mean age was 25.3±2.4 y. There were slightly more males (50.7%). Most attended universities (77.8%) and were mainly from the southwest (24.5%) and northeast (24.5%) geopolitical regions and the Yoruba tribe (24.7%). Their lifetime prevalence of snakebite was 4%. Their mean overall knowledge score was 6.8±3.1 out of 20. Only 0.9% had adequate knowledge. Gender (male; 7.2±3.1, t=2.83, p=0.0049), tribe (Yoruba; 7.5±2.9, F=2.968, p=0.0320), region (Southwest; 7.6±3.0, F=2.5289, p=0.0289) and nearly bitten by snake (7.8 ± 2.7, t=3.60, p=0.0004) were significantly associated with a higher mean knowledge score. CONCLUSIONS: Their lifetime prevalence of snakebites is significant, while knowledge of snakebite is very inadequate. However, the national service camp activities period provides an opportunity for educational intervention needed to raise their knowledge to optimal levels that will enable them serve as better snakebite prevention agents, as they will be working in rural communities where snakebite might be prevalent.

Performance of the 20 minutes Whole Blood Clotting Test in detection, monitoring and antivenom therapy of West African Carpet viper (Echis romani) envenoming in resource constrained settings in Nigeria.

The 20 minutes Whole Blood Clotting Test (20WBCT) was evaluated in 1541 snakebite patients at 3 hospitals in Nigeria. It was useful in detection, monitoring, guiding antivenom therapy and prognostication of coagulopathy, with initial sensitivity of 84.7% (95%CI:82.7-86.5%) and specificity of 64.3% (95%CI:50.4-76.7%) compared to clinical envenoming. It led to correct decisions regarding administration or withholding antivenom in 97.93% of patients. The proportion of carpet viper (Echis romani) envenomed patients who restored clotting rose steadily following effective antivenom therapy. Patients with positive 20WBCT had severer envenoming, required more blood transfusion, had longer hospital stay and derived higher antivenom protection against death from carpet viper. However, there was no association between positive 20WBCT and fatality or complications.

Case fatality rate and burden of snakebite envenoming in children - A systematic review and meta-analysis.

Snakebite is a major public health problem with an estimated global burden of 5 million people per annum. Data on snakebite envenoming in children are very limited and is unclear whether there is a significant difference in severity between adults and children. We therefore conducted a meta-analysis of observational studies on snakebite in children to obtain a more precise estimate of case fatality rate (CFR) as well as to explore the differences in outcome between children and adults. Studies from all over the world reported until the end of February 2023 were included. Analysis was conducted consistent with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria. Estimates were obtained from Random Effects Model (REM). Sub-analysis was conducted for studies from sub-Saharan Africa (SSA) to provide estimates for the continent. Adverse outcomes comprising composite endpoints (CE), defined as fatality and or complications, were compared between children and adults in sub-analysis of studies reporting on both groups. The annual burden and fatality of snakebite envenoming were derived based on lifetime prevalence of bite, meta-analysis estimates, and other data inputs. The pooled estimate of the CFR from 35 studies included worldwide was 1.98% [95%CI:1.38-2.58%] while the estimates from 6 studies within SSA was 2.43% (95%CI:0.67-4.20%). The odds of adverse outcomes were 2.52 times higher in children compared to adults. The estimated annual burden was 178,491 cases with 4346 deaths among children in SSA. These estimates compare favorably to those reported in the literature.

A prospective observational phase IV study on effectiveness of animal derived polyclonal antibody antivenoms against West African carpet viper (Echis romani) induced coagulopathy and mortality.

Conventional polyclonal antibody antivenoms are the mainstay of snakebite therapy. They have not been proven to be efficacious in randomized placebo controlled clinical trials among severely envenomed patients. There is also paucity of evidence on effectiveness especially in routine use. The current study evaluated their effectiveness in post marketing use among those managed with and without antivenom as regards to reversal of venom induced coagulopathy defined using the 20 min Whole Blood Clotting Test [20WBCT] and in averting death. The effectiveness of antivenom was evaluated among 5467 patients predominantly envenomed by the West African carpet viper (Echis romani) at 3 hospitals in Nigeria from 2021 to 2022. Two antivenoms Echitab G (EG) and Echitab ICP Plus (EP) were able to restore normal clotting within 6 h of administration in 58.0% [95% Confidence Interval (95%CI)] (51.2-64.5%) and 91.7% (90.4-93.0%) of patients respectively. They were able to restore normal clotting within 24 h of administration in 96.9% (94.0-98.7%) and 99.0% (98.4-99.4%) of patients respectively. The Odds Ratio [OR (95%CI)] of dying among patients with positive 20WBCT who were treated with ≥1 vial of either EG or EP compared to those not treated was 0.06 (0.02-0.23) and 0.07 (0.03-0.15) respectively. This equated to antivenom protection against in-hospital mortality of 93-94% among patients with confirmed coagulopathy though the benefit appeared abrogated among those without coagulopathy. The untreated natural mortality was 15.94% (95%CI:8.24-26.74%) without antivenom therapy while the overall mortality was 84/5105 (1.65%; 95%CI:1.32-2.03%. The Number Needed to Treat (NNT) to avert a death was 7 patients among those with coagulopathy. Antivenoms were safe with mild early adverse reactions observed among 2.6% (95%CI:2.13-3.08%) of antivenom recipients. Polyclonal antibody antivenoms are effective and safe for treating coagulopathic envenomed patients in Nigeria.

Comparison of snakebite in children and adults in Nigeria.

Snakebite envenoming is a major global public health problem and disproportionately affects children. To study the differences in clinical presentation and outcomes between children and adults, 2922 snakebite patients of whom 30.3% were children were analysed. Most bites (>75%) were in the lower. Features of local envenoming were commoner among children compared to adults (p < 0.05), while systemic envenoming features, mortality and complications were similar, p = 0.356, p = 0.12, and p = 0.16 respectively.

Stakeholder perspectives from 15 countries in Africa on barriers in snakebite envenoming research and the potential role of research hubs.

Snakebite envenoming is a debilitating neglected tropical disease disproportionately affecting the rural poor in low and middle-income countries in the tropics and sub-tropics. Critical questions and gaps in public health and policy need to be addressed if major progress is to be made towards reducing the negative impact of snakebite, particularly in the World Health Organisation (WHO) Africa region. We engaged key stakeholders to identify barriers to evidence-based snakebite decision making and to explore how development of research and policy hubs could help to overcome these barriers. We conducted an electronic survey among 73 stakeholders from ministries of health, health facilities, academia and non-governmental organizations from 15 countries in the WHO Africa region. The primary barriers to snakebite research and subsequent policy translation were limited funds, lack of relevant data, and lack of interest from policy makers. Adequate funding commitment, strong political will, building expert networks and a demand for scientific evidence were all considered potential factors that could facilitate snakebite research. Participants rated availability of antivenoms, research skills training and disease surveillance as key research priorities. All participants indicated interest in the development of research and policy hubs and 78% indicated their organization would be willing to actively participate. In conclusion, our survey affirms that relevant stakeholders in the field of snakebite perceive research and policy hubs as a promising development, which could help overcome the barriers to pursuing the WHO goals and targets for reducing the burden of snakebite.

Diagnostic characteristics of the 20-minute whole blood clotting test in detecting venom-induced consumptive coagulopathy following carpet viper envenoming.

INTRODUCTION: Envenoming by Echis spp. (carpet or saw-scaled vipers) causes haemorrhage and coagulopathy and represents a significant proportion of snakebites in the savannah regions of West Africa. Early diagnosis of envenoming is crucial in the management of these patients and there is limited evidence on the utility of the 20-minute whole blood clotting test (20WBCT) in diagnosing venom-induced consumptive coagulopathy (VICC) following envenoming by Echis ocellatus. METHODS: A prospective observational cohort study was conducted at the Kaltungo General Hospital in North-eastern Nigeria from September 2019 to September 2021. Standardised 20WBCTs were conducted by trained hospital staff and citrated plasma samples were collected at numerous timepoints. Prothrombin time (PT) and international normalised ratio (INR) were determined using a semi-automated analyser and INR values were calculated using international sensitivity indices (ISI). The sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and likelihood ratios of the 20WBCT compared to an INR ≥ 1.4 were calculated, alongside 95% confidence intervals. RESULTS: We enrolled 121 patients into our study, with a median age of 26 (18.0-35.0) years and a male predominance (75.2%). The 20WBCT was positive (abnormal) in 101 out of 121 patients at timepoint 0h, of which 95 had an INR ≥ 1.4, giving a sensitivity of 87.2% (95%CI 79.4-92.8). Among patients with a negative 20WBCT (normal), six had an INR < 1.4 giving a specificity of 50% (95%CI 21.1-78.9). The positive and negative likelihood ratios were 1.7 (95%CI 1.6-1.9) and 0.3 (95%CI 0.1-0.4) respectively. CONCLUSION: The 20WBCT is a simple, cheap, and easily accessible bedside test with a high sensitivity for the detection of patients with venom induced consumptive coagulopathy (VICC) following envenoming by E. ocellatus, although false positives do occur. Repeated 20WBCTs can identify patients with new, persistent, and rebound coagulopathy.

A global core outcome measurement set for snakebite clinical trials.

Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials-mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

[A global core outcome measurement set for snakebite clinical trials]. / Définition d'un jeu universel de critères de décision de base pour les essais cliniques sur les morsures de serpent.

Background: Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. Method: A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Results: Five universal core outcome measures should be included in all future snakebite clinical trials: mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. Conclusion: This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

Clinical features and preliminary studies of virological correlates of neurocognitive impairment among HIV-infected individuals in Nigeria.

In Nigeria, the incidence and prevalence of human immunodeficiency virus (HIV)-related neurocognitive impairment (NCI) are unknown and there currently exists little information related to the viral correlates rates of NCI. Therefore, studies were performed to examine the potential utility of applying an established neuropsychological (NP) screening battery and detailed NP testing to detect NCI and correlations with functional impairment and the presence of specific viral signatures among infected subjects. A total of 60 HIV-1 seropositive antiretroviral-naive individuals and 56 seronegative control subjects were administered the International HIV Dementia Scale (IHDS) and assessed for functional impairment using the Karnofsky performance status scale. Fifteen HIV-infected patients and 11 controls were also administered a detailed NP battery. Blood samples from eight infected subjects, three with evidence of NCI, were obtained for molecular analysis of HIV-1 strain. Unadjusted scores on the IHDS showed that, using a recommended total score cutoff of 10, 28.8% of the HIV-1 seropositive and 16.0% of seropositive individuals scored abnormally. Results from testing using the full NP battery showed that, overall, the HIV seropositive group performed worse than the seronegative group, with effect sizes spanning from small (0.25 on the trail making test A) to large (0.82 on action fluency), and an average effect size across the battery of 0.45, which approaches that which has been recorded in other international settings. Sequencing of partial pol amplicons from viral isolates revealed that two of three patients with NCI were infected with subtype G virus and 1 with the circulating recombinant form (CRF)02_AG; all four individuals without NCI were infected with CRF_02AG. These studies demonstrate the utility of the IHDS in identifying cognitive impairment among HIV infected individuals in Nigeria. Future studies aimed at examining the burden of NCI among the population of individuals with HIV-1 infection in Nigeria and which assess the virologic correlates will contribute to the evolving understanding of the pathogenetic factors that underlie this disorder.