Metagenomic sequencing characterizes a wide diversity of viruses in field mosquito samples in Nigeria.

Mosquito vectors are a tremendous public health threat. One in six diseases worldwide is vector-borne transmitted mainly by mosquitoes. In the last couple of years, there have been active Yellow fever virus (YFV) outbreaks in many settings in Nigeria, and nationwide, entomological surveillance has been a significant effort geared towards understanding these outbreaks. In this study, we used a metagenomic sequencing approach to characterize viruses present in vector samples collected during various outbreaks of Yellow fever (YF) in Nigeria between 2017 and 2020. Mosquito samples were grouped into pools of 1 to 50 mosquitoes, each based on species, sex and location. Twenty-five pools of Aedes spp and one pool of Anopheles spp collected from nine states were sequenced and metagenomic analysis was carried out. We identified a wide diversity of viruses belonging to various families in this sample set. Seven different viruses detected included: Fako virus, Phasi Charoen-like virus, Verdadero virus, Chaq like-virus, Aedes aegypti totivirus, cell fusing agent virus and Tesano Aedes virus. Although there are no reports of these viruses being pathogenic, they are an understudied group in the same families and closely related to known pathogenic arboviruses. Our study highlights the power of next generation sequencing in identifying Insect specific viruses (ISVs), and provide insight into mosquito vectors virome in Nigeria.

A standardised Phase III clinical trial framework to assess therapeutic interventions for Lassa fever.

BACKGROUND: Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. METHODOLOGY: We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. RESULTS: A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. CONCLUSIONS: This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.

Early onset of neurological features differentiates two outbreaks of Lassa fever in Ebonyi state, Nigeria during 2017-2018.

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.

Human Monkeypox in Sierra Leone after 44-Year Absence of Reported Cases.

We note the reemergence of human monkeypox in Sierra Leone following a 44-year absence of reported disease. The persons affected were an 11-month-old boy and, several years later, a 35-year-old man. The reappearance of monkeypox in this country suggests a need for renewed vigilance and awareness of the disease and its manifestations.

Offering general pediatric care during the hard times of the 2014 Ebola outbreak: looking back at how many came and how well they fared at a Médecins Sans Frontières referral hospital in rural Sierra Leone.

BACKGROUND: In Bo district, rural Sierra Leone, we assessed the burden of the 2014 Ebola outbreak on under-five consultations at a primary health center and the quality of care for under-15 children at a Médecins Sans Frontières (MSF) referral hospital. METHODS: Retrospective cohort study, comparing a period before (May-October 2013) and during the same period of the Ebola outbreak (2014). Health worker infections occurred at the outbreak peak (October 2014), resulting in hospital closure due to fear of occupational-risk of contracting Ebola. Standardized hospital exit outcomes and case fatality were used to assess quality of care until closure. RESULTS: A total of 13,658 children under-five, were seen at the primary health center during 2013 compared to 8761 in 2014; a consultation decline of 36%. Of 6497 children seen in the hospital emergency room, during the outbreak, patients coming from within hospital catchment area declined with 38% and there were significantly more self-referrals (80% vs. 61%, P < 0.001). During Ebola, 23 children were dead on arrival and the proportion of children in severe clinical status (requiring urgent attention) was higher (74% during Ebola vs. 65% before, P < 0.001). Of 5,223 children with available hospital outcomes, unfavorable outcomes (combination of deaths and abandoned) were less than 15% during both periods, which is within the maximum acceptable in-house threshold set by MSF. Case fatality for severe malaria and lower respiratory tract infections (n = 3752) were similar (≤15%). CONCLUSIONS: Valuable and good quality pediatric care was being provided in the pediatric hospital during the 2014 Ebola outbreak, but could not be sustained because of hospital closure. Health facility and health worker safety should be tackled as a universal requirement to try to avoid a déjà-vu.

Unregulated usage of labour-inducing medication in a region of Pakistan with poor drug regulatory control: characteristics and risk patterns.

BACKGROUND: In developing countries such as Pakistan, poor training of mid-level cadres of health providers, combined with unregulated availability of labour-inducing medication can carry considerable risk for mother and child during labour. Here, we describe the exposure to labour-inducing medication and its possible risks in a vulnerable population in a conflict-affected region of Pakistan. METHODS: A retrospective cohort study using programme data, compared the outcomes of obstetric risk groups of women treated with unregulated oxytocin, with those of women with regulated treatment. RESULTS: Of the 6379 women included in the study, 607 (9.5%) received labour-inducing medication prior to reaching the hospital; of these, 528 (87.0%) received unregulated medication. Out of 528 labour-inducing medication administrators, 197 (37.3%) traditional birth attendants (also known as dai) and 157 (29.7%) lady health workers provided unregulated treatment most frequently. Women given unregulated medication who were diagnosed with obstructed/prolonged labour were at risk for uterine rupture (RR 4.1, 95% CI: 1.7-9.9) and severe birth asphyxia (RR 3.9, 95% CI: 2.5-6.1), and those with antepartum haemorrhage were at risk for stillbirth (RR 1.8, 95% CI: 1.0-3.1). CONCLUSIONS: In a conflict-affected region of Pakistan, exposure to unregulated treatment with labour-inducing medication is common, and carries great risk for mother and child. Tighter regulatory control of labour-inducing drugs is needed, and enhanced training of the mid-level cadres of healthcare workers is required.

Reliability and accuracy of the South African Triage Scale when used by nurses in the emergency department of Timergara Hospital, Pakistan.

BACKGROUND: Triage is one of the core requirements for the provision of effective emergency care and has been shown to reduce patient mortality. However, in low- and middle-income countries this strategy is underused, under-resourced and poorly researched. OBJECTIVE: To assess the inter- and intra-rater reliability and accuracy of nurse triage ratings when using the South African Triage Scale (SATS) in an emergency department (ED) in Timergara, Pakistan. METHODS: Fifteen ED nurses assigned triage ratings to a set of 42 reference vignettes (written case reports of ED patients) under classroom conditions. Inter-rater reliability was assessed by comparing these triage ratings; intra-rater reliability was assessed by asking the nurses to re-triage 10 random vignettes from the original set of 42 vignettes and comparing these duplicate ratings. Accuracy of the nurse ratings was measured against the reference standard. RESULTS: Inter-rater reliability was substantial (intraclass correlation coefficient 0.77; 95% confidence interval (CI) 0.69 - 0.85). The intra-rater agreement was also high with 87% exact agreement (95% CI 67 - 100) and 100% agreement allowing for a one-level discrepancy in triage ratings. Overall, the SATS had high specificity (97%) and moderate sensitivity (70%). Across all acuity levels the proportion of over-triage did not exceed the acceptable threshold of 30 - 50%. Under-triage was acceptable for all except emergency cases (66%). CONCLUSION: ED nurses in Pakistan can reliably use the SATS to assign triage acuity ratings. While the tool is accurate for 'very urgent' and 'routine' cases, importantly, it may under-triage 'emergency' cases requiring immediate attention. Approaches that will improve accuracy and validity are discussed.

Offering mental health services in a conflict affected region of Pakistan: who comes, and why?

BACKGROUND: North West Pakistan is an area ravaged by conflict and population displacement for over three decades. Recently, drone attacks and military operations have aggravated underlying mental disorders, while access to care is limited. Among patients attending a mental health clinic integrated in district hospital conducted by psychologists; we describe service utilization, patient characteristics, presenting complaints, morbidity patterns, and follow-up details. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study using routinely collected programme data was conducted from February to December 2012. A total of 1545 consultations were conducted for 928 patients (86% females). There were 71(8%) children and adolescents. An increase was observed from February to July, followed by a decline. 163 new patients (18%) were on psychotropic medication at presentation. The most common morbidity in females (36%) were symptoms of adjustment disorders and acute reactions. Depression and anxiety were common in both genders while post traumatic disorder was frequent in males (21%). Out of the 928 new patients, 639(69%) had a follow up visit planned with their psychologist, but only 220(34%) new patients returned for a follow up visit. CONCLUSION: In a district hospital, mental health services managed by psychologists were well attended. There is a need to consider widening the current package of care to cater to the diversity of mental health disorders, gender difference, children and adolescents. Standardized diagnostic and monitoring tools would also need to be adapted accordingly and to assess patient progress. Innovative approaches to tackle the problem of the low return rate are needed.

Distribution of antiretroviral treatment through self-forming groups of patients in Tete Province, Mozambique.

BACKGROUND: As antiretroviral treatment cohorts continue to expand, ensuring patient retention over time is an increasingly important concern. This, together with capacity and human resource constraints, has led to the consideration of out-of-clinic models for the delivery of antiretroviral therapy (ART). In 2008, Médecins Sans Frontières and the Provincial authorities launched a model of ART distribution and adherence monitoring by community groups in Tete Province, Mozambique. PROGRAMME APPROACH: Patients who were stable on ART for 6 months were informed about the community ART group model and invited to form groups. Group members had 4 key functions: facilitate monthly ART distribution to other group members in the community, provide adherence and social support, monitor outcomes, and ensure each group member undergoes a clinical consultation at least once every 6 months. Group members visit the health centre on a rotational basis, such that each group member has contact with the health service every 6 months. RESULTS: Between February 2008 and May 2010, 1384 members were enrolled into 291 groups. Median follow-up time within a group was 12.9 months (IQR 8.5-14.1). During this time, 83 (6%) were transferred out, and of the 1301 patients still in community groups, 1269 (97.5%) were remaining in care, 30 (2%) had died, and 2 (0.2%) were lost to follow-up. DISCUSSION: The Community ART Group model was initiated by patients to improve access, patient retention, and decongest health services. Early outcomes are highly satisfactory in terms of mortality and retention in care, lending support to such out-of-clinic approaches.

Challenges in mass drug administration for treating lymphatic filariasis in Papua, Indonesia.

BACKGROUND: The World Health Organization (WHO) Global Program to Eliminate Lymphatic Filariasis relies on mass drug administration (MDA) of two drugs annually for 4 to 6 years. The goal is to reduce the reservoir of microfilariae in the blood to a level insufficient to maintain transmission by the mosquito vector. In 2008, the international medical aid organization Médecins Sans Frontières (MSF) performed the first round of a MDA in the high-burden area of Asmat district, in Papua, Indonesia. We report the challenges faced in this MDA on a remote Indonesian island and propose solutions to overcome these hurdles in similar future contexts. RESULTS: During the MDA, we encountered difficult challenges in accessing as well as persuading the patient population to take the antifilarial drugs. Health promotion activities supporting treatment need to be adapted and repetitive, with adequate time and resources allocated for accessing and communicating with local, seminomadic populations. Distribution of bednets resulted in an increase in MDA coverage, but it was still below the 80-85% target. CONCLUSIONS: MDA for lymphatic filariasis is how the WHO has planned to eliminate the disease from endemic areas. Our programmatic experience will hopefully help inform future campaign planning in difficult-to-access, high-burden areas of the world to achieve target MDA coverage for elimination of lymphatic filariasis.

Successful introduction of artesunate combination therapy is not enough to fight malaria: results from an adherence study in Sierra Leone.

A study to measure adherence to artesunate and amodiaquine (AS+AQ) therapy in patients treated for uncomplicated malaria in community health centres (CHC) was conducted in Sierra Leone. Patients/caretakers were interviewed and remaining AS+AQ tablets at home after the last treatment dose were counted. Persons leaving CHCs with an AS+AQ prescription were also interviewed (exit interviews). In total, 118 patients were visited at home: 27 (22.9%) had one or more tablets left and were classed as certainly non-adherent; 34 (28.8%) were probably non-adherent [reported incorrect (n=27) or incomplete (n=7) intake]; and 57 (48.3%) were probably adherent. The main reasons for incomplete intake were sickness after one dose of AS+AQ, no food available for drug intake and forgetting to take them. For incorrect intake, reasons were vomiting after drug intake and incorrect instructions given by the CHC. Eighty-one percent of probably adherent patients reported following instructions given to them. In exit interviews, 82% of patients or caretakers of patients were able to repeat AS+AQ intake instructions correctly. Adherence to antimalarial treatment should not be taken for granted. Instructions on correct AS+AQ use should include discussion of disease symptoms as well as possible treatment side effects and how to manage them. Other factors are more difficult to influence, such as patients forgetting to take the treatment.

Long-lasting insecticide-treated net usage in eastern Sierra Leone - the success of free distribution.

OBJECTIVE: Médecins Sans Frontières (MSF) runs a malaria control project in Bo and Pujehun districts (population 158 000) that includes the mass distribution, routine delivery and demonstration of correct use of free, long-lasting insecticide-treated nets (LLINs). In 2006/2007, around 65 000 LLINs were distributed. The aim of this follow-up study was to measure LLIN usage and ownership in the project area. METHODS: Heads of 900 randomly selected households in 30 clusters were interviewed, using a standardized questionnaire, about household use of LLINs. The condition of any LLIN was physically assessed. RESULTS: Of the 900 households reported, 83.4% owning at least one LLIN. Of the 16.6% without an LLIN, 91.9% had not participated in the MSF mass distribution. In 94.1% of the households reporting LLINs, the nets were observed hanging correctly over the beds. Of the 1135 hanging LLINs, 75.2% had no holes or 10 or fewer finger-size holes. The most common source of LLINs was MSF (75.2%). Of the 4997 household members, 67.2% reported sleeping under an LLIN the night before the study, including 76.8% of children under 5 years and 73.0% of pregnant women. CONCLUSION: Our results show that MSF achieved good usage with freely distributed LLINs. It is one of the few areas where results almost achieve the new targets set in 2005 by Roll Back Malaria to have at least 80% of pregnant women and children under 5 years using LLINs by 2010.

Assessment of two malaria rapid diagnostic tests in children under five years of age, with follow-up of false-positive pLDH test results, in a hyperendemic falciparum malaria area, Sierra Leone.

BACKGROUND: Most malaria rapid diagnostic tests (RDTs) use HRP2 detection, including Paracheck-Pf(R), but their utility is limited by persistent false positivity after treatment. PLDH-based tests become negative more quickly, but sensitivity has been reported below the recommended standard of 90%. A new pLDH test, CareStart three-line P.f/PAN-pLDH, claims better sensitivity with continued rapid conversion to negative. The study aims were to 1) compare sensitivity and specificity of CareStart to Paracheck-Pf(R) to diagnose falciparum malaria in children under five years of age, 2) assess how quickly false-positive CareStart tests become negative and 3) evaluate ease of use and inter-reader agreement of both tests. METHODS: Participants were included if they were aged between two and 59 months, presenting to a Médecins Sans Frontières community health centre in eastern Sierra Leone with suspected malaria defined as fever (axillary temperature > 37.5 degrees C) and/or history of fever in the previous 72 hours and no signs of severe disease. The same capillary blood was used for the RDTs and the blood slide, the latter used as the gold standard reference. All positive participants were treated with supervised artesunate and amodiaquine treatment for three days. Participants with a persistent false-positive CareStart, but a negative blood slide on Day 2, were followed with repeated CareStart and blood slide tests every seven days until CareStart became negative or a maximum of 28 days. RESULTS: Sensitivity of CareStart was 99.4% (CI 96.8-100.0, 168/169) and of Paracheck-Pf(R), 98.8% (95% CI 95.8-99.8, 167/169). Specificity of CareStart was 96.0% (CI 91.9-98.4, 167/174) and of Paracheck-Pf(R), 74.7% (CI 67.6-81.0, 130/174) (p < 0.001). Neither test showed any change in sensitivity with decreasing parasitaemia. Of the 155 eligible follow-up CareStart participants, 63.9% (99/155) had a false-positive test on day 2, 21.3% (33/155) on day 7, 5.8% (9/155) on day 14, 1.9% (3/155) on day 21 and 0.6% (1/155) on day 28. The median time for test negativity was seven days. CareStart was as easy to use and interpret as Paracheck-Pf(R) with excellent inter-reader agreement. CONCLUSIONS: Both RDTs were highly sensitive, met WHO standards for the detection of falciparum malaria monoinfections where parasitaemia was >100 parasites/mul and were easy to use. CareStart persistent false positivity decreased quickly after successful anti-malarial treatment, making it a good choice for a RDT for a hyperendemic falciparum malaria area.

Efficacy of chloroquine, sulfadoxine-pyrimethamine and amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria among children under five in Bongor and Koumra, Chad.

We report two 28-day in-vivo antimalarial efficacy studies carried out in the urban centres of Bongor and Koumra, southern Chad. We assess chloroquine (CQ), sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) to treat Plasmodium falciparum uncomplicated malaria. Methods and outcome classification complied with latest WHO guidelines. Out of the 301 and 318 children aged 6-59 months included in Bongor and Koumra, respectively, 246 (81.7%) and 257 (80.8%) were eligible for analysis. In Bongor and Koumra, the 28-day PCR-adjusted failure rates for CQ were 23.7% (95% CI 14.7-34.8%) and 32.9% (95% CI 22.1-45.1%), respectively, and those for SP were 16.3% (95% CI 9.4-25.5%) and 4.3% (95% CI 1.2-10.5%). AQ failure rates were 6.4% (95% CI 2.1-14.3%) and 2.2% (95% CI 0.3-7.6%). The current use of CQ in Bongor and Koumra is questionable, and a more efficacious treatment is needed. Considering the reduced efficacy of SP in Bongor, AQ seems to be the best option for the time being. Following WHO recommendations that prioritize the use of artemisinin-based combinations, artesunate plus amodiaquine could be a potential first-line treatment. Nevertheless, the efficacy of this combination should be evaluated and the change carefully prepared, implemented and monitored.