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Background In low-resource settings, inflammatory biomarkers can help identify patients with acute febrile illness who do not require antibiotics. Their use has not been studied in persistent fever (defined as fever lasting for ≥7 days at presentation). Methods C-reactive protein (CRP) and procalcitonin (PCT) levels were measured in stored serum samples of patients with persistent fever prospectively enrolled in Cambodia, the Democratic Republic of Congo, Nepal, and Sudan. Diagnostic accuracy was assessed for identifying all bacterial infections and the subcategory of severe infections judged to require immediate antibiotics. Results Among 1838 participants, CRP and PCT levels were determined in 1777 (96.7%) and 1711 (93.1%) samples, respectively, while white blood cell (WBC) count was available for 1762 (95.9%). Areas under the receiver operating characteristic curve for bacterial infections were higher for CRP (0.669) and WBC count (0.651) as compared with PCT (0.600; P <.001). Sensitivity for overall and severe bacterial infections was 76.3% (469/615) and 88.2% (194/220) for CRP >10 mg/L, 62.4% (380/609) and 76.8% (169/220) for PCT >0.1 µg/L, and 30.5% (184/604) and 43.7% (94/215) for WBC >11 000/µL, respectively. Initial CRP level was <10 mg/L in 45% of the participants who received antibiotics at first presentation. Conclusions In patients with persistent fever, CRP and PCT showed higher sensitivity for bacterial infections than WBC count, applying commonly used cutoffs for normal values. A normal CRP value excluded the vast majority of severe infections and could therefore assist in deciding whether to withhold empiric antibiotics after cautious clinical assessment. [ABSTRACT FROM AUTHOR]

Introduction. Before the introduction of vaccination to protect children from pneumonia, Streptococcus pneumoniae and Haemophilus influenzae type B (HiB) were the most frequent aetiological agents causing bacterial pneumonia in children under five years old. However, the etiology of childhood pneumonia appears to be changing and nonvaccine- type S. pneumoniae, non-typeable H. influenzae, and Staphylococcus aureus are becoming more relevant. Objective. We conducted a systematic review aimed at identifying the common causes of bacterial pneumonia in children in sub-Saharan Africa. Methods. We searched PubMed, Web of Science and African Index Medicus and included primary studies conducted since January 2010 that reported on the bacterial causes of pneumonia in children under five from sub-Saharan Africa. We extracted data items (about the study setting, pneumonia diagnosis, sampling, microbiological methods, and etiological agents) as well as study quality indicators. Results. Streptococcus pneumoniae was the most common bacteria in blood cultures from children with pneumonia (8%, 95% CI: 4-14%), and H. influenzae was second (3%, 95% CI: 1-17%). Children's nasopharynx commonly contained S. pneumoniae (66%), Moraxella catarrhalis (62%), and H. influenzae (44%). Conclusion. S. pneumoniae and H. influenzae cause bacterial pneumonia in sub-Saharan African children. Our review also highlights the prevalence of potentially pathogenic bacteria in the nasopharynx of children under five and calls for more research into how nasopharyngeal colonization causes pneumonia. [ABSTRACT FROM AUTHOR]

Background: Podoconiosis is a skin Neglected Tropical Disease (skin NTD) that causes lymphoedema, and affects barefooted subsistence farmers in some tropical countries. The clinical presentation and histopathologic correlates of podoconiosis have been understudied. Here, we systematically document the clinical and histopathologic spectrum of podoconiosis. Methods: This is a cross-sectional study in Durbete, Ethiopia from February 2018 to October 2019. Dermatologists performed a patient history, physical examination, filariasis test strip, and skin biopsy for histopathologic examination. The results were summarised and a descriptive statistical analysis and Wilcoxon rank sum test with continuity correction was done. Results: We recruited 289 patients for the study, 178 (61.6%) had stage 1 or 2 podoconiosis, and 111(38.4%) stage 3 to 5 podoconiosis. 188 (64.1%) had a family history of podoconiosis. In 251 (86.9%) patients, both legs were affected by podoconiosis and in 38 (13.1%) only one leg was affected. 220 (77.5%) patients had warty lesions, 114 (39.4%) had nodules. The median number of episodes of Acute Dermato-Lymphangio-Adenitis (ADLA) reported by the patients in the last three months was 2 (interquartile range (IQR) 1–4). Increased episodes of ADLA were significantly associated with stage 3–5 podoconiosis (P = 0.002), while burning pain in the feet was more common in stage 1 or 2 podoconiosis. Stage 3–5 disease was histopathologically characterised by epidermal and dermal thickening, verrucous acanthosis, inflammatory cell infiltrates (predominantly lymphoplasmacytic), dilated and ectatic and a reduced number of lymphatic vessels, eccrine ductal hyperplasia, and sclerosis such as thickened collagen bundles. Conclusion: We provide a detailed description of the different clinical patterns, associated clinical findings and the histopathologic spectrum of podoconiosis at different stages of the disease. Our observations should serve as a guide to classifying patients with podoconiosis for prognostic assessment and treatment decision. Author summary: Podoconiosis is a skin Neglected Tropical Disease (skin NTD) that causes swelling of the lower extremities. The disease affects barefooted subsistence farmers in some tropical countries. It is caused by destruction of the lymphatic system in the legs, which is critical for the transportation of body fluids. Podoconiosis is physically disabling with significant psycho-social impact. In Ethiopia alone more than 1.5 million people are affected by podoconiosis. The past 50 to 60 years generated substantial evidence on the disease distribution, genetic influence, psycho-social impact and clinical management. Yet, systematic information about the various clinical manifestations and histopathologic features of podoconiosis is sparse. We therefore recorded in 289 podoconiosis patients their history, and disease-related findings of the lower extremities. We also took blood and tissue samples for laboratory examination. In summary, this study provides a description of the different clinical manifestations and microscopic tissue findings of various podoconiosis stages from mild to advance. Our observations are a guide to classifying patients with podoconiosis, based on clinical and microscopic tissue definitions. Classification can help in patient management, therapeutic follow-up, prioritisation of resources, epidemiological surveillance and future research to improve the quality of life of patients with podoconiosis. [ABSTRACT FROM AUTHOR]

Background: A high prevalence of epilepsy has been observed in several onchocerciasis-endemic villages in the Sanaga River basin, Cameroon. Recent studies suggest that ivermectin, a drug that is distributed annually with the aim of eliminating onchocerciasis, may have a protective effect against acquiring onchocerciasis-associated epilepsy (OAE). This study, therefore, provides an in-depth understanding of both the complex therapeutic landscape for epilepsy as well as the experiences related to the 'community-directed treatment with ivermectin' (CDTI) campaign in order to identify a more trenchant path forward in the fight against epilepsy. Methodology/Principal findings: Based on a mixed methods study combining a qualitative strand with a quantitative survey, we found that epilepsy was perceived to have had an epidemic emergence in the past and was still considered an important health issue in the study area. Socio-economic status, availability and accessibility of drugs and practitioners, as well as perceived aetiology shaped therapeutic itineraries for epilepsy, which included frequenting (in)formal biomedical health care providers, indigenous and/or faith healing practitioners. Ivermectin uptake for onchocerciasis was generally well known and well regarded. The CDTI faced structural and logistical bottlenecks undermining equal access and optimal adherence to the drug. Conclusions/Significance: Uninterrupted, sustainable and comprehensive health-service delivery is essential to help alleviate the epilepsy burden on afflicted households. Addressing structural challenges of CDTI and communicating the potential link with epilepsy to local populations at risk could optimize the uptake of this potentially significant tool in OAE prevention. Author summary: Regions where onchocerciasis–a parasitical infection transmitted by blackflies–is endemic also tend to suffer from high levels of epilepsy. Recent studies suggest that ivermectin, an anti- onchocerciasis drug distributed annually to entire populations in onchocerciasis-endemic regions, may protect against developing onchocerciasis-associated epilepsy (OAE). As the link between onchocerciasis and epilepsy has been poorly understood and scientifically neglected in the past, our mixed methods research investigated how residents in an affected Cameroonian area perceive and cope with epilepsy; how they interpret the (causes of the) illness; where they seek care and why there. Armed with this knowledge, epilepsy control programs can optimize interventions geared at relieving the burden of epilepsy–and potentially OAE–which is essential given the fact that, despite 15–20 years of ivermectin distribution, onchocerciasis transmission persists and epilepsy prevalence in these regions remains high. Our findings illustrate how crucial it is to ensure uninterrupted, sustainable and comprehensive health service delivery for epilepsy. Furthermore, the structural challenges associated with the mass ivermectin distribution campaign must be addressed in order to relieve the burden of onchocerciasis, and potentially OAE. Without first addressing these structural bottlenecks, uptake and adherence to ivermectin treatment will remain insufficient. [ABSTRACT FROM AUTHOR]

Background: In Ethiopia, severe lymphedema and acute dermato-lymphangio-adenitis (ADLA) of the legs as a consequence of podoconiosis affects approximately 1.5 million people. In some this condition may lead to woody-hard fibrotic nodules, which are resistant to conventional treatment. We present a series of patients who underwent surgical nodulectomy in a resource-limited setting and their outcome. Methods: In two teaching hospitals, we offered surgical nodulectomies under local anaesthesia to patients with persisting significant fibrotic nodules due to podoconiosis. Excisions after nodulectomy were left to heal by secondary intention with compression bandaging. As outcome, we recorded time to re-epithelialization after surgery, change in number of ADLA episodes, change in quality of life measured with the Dermatology Quality of Live Index (DQLI) questionnaire, and recurrence rate one year after surgery. Results: 37nodulectomy operations were performed on 21 patients. All wounds re-reepithelialised within 21 days (range 17–42). 4 patients developed clinically relevant wound infections. The DLQI values were significantly better six months after surgery than before surgery (P<0.0001). Also the number of ADLA episodes per three months was significantly lower six months after surgery than before surgery (P<0.0001). Conclusion: Nodulectomy in podoconiosis patients leads to a significant improvement in the quality of life with no serious complications, and we recommend this to be a standard procedure in resource-poor settings. Author summary: Podoconiosis is a disease that causes swelling of the lower legs and tissue lumps (nodules) of the feet. The condition is physically disabling with significant psycho-social impact. It is caused by the destruction of the lymphatic system, that is critical in the transportation of body fluids. The disease is said to be caused by long term barefooted exposure to red-clay soil. Podoconiosis affects more than four million subsistent farmers in the tropics. Ethiopia is one of the endemic countries with more than 1.5 million affected people. Early-stage podoconiosis morbidity management consists of foot hygiene, regular inspection and care for traumatic abrasions, use of moisturizer, daily exercise, compression with elastic bandages, and last but not least shoe wearing. In the late disease stage, irreversible swelling and woody-hard fibrous nodules arise. As a result, patients can no longer wear shoes and suffer from disabling bacterial infection. Both complications aggravate lymphatic destruction. Moreover, late-stage podoconiosis is unresponsive to the aforementioned therapy options. Surgical intervention removing the nodules (nodulectomy) can potentially alleviate late-stage disease. Here, we describe the clinical outcome of nodulectomy and its effect on the quality of life in 21 late stage podoconiosis patients, in a before to 12 months after the procedure comparison. We demonstrate that nodulectomy is safe, allows patients to wear shoes again, reduces the number of bacterial infections, and significantly improves their quality of life. Nodulectomy is a safe and effective procedure for podoconiosis patients. We recommend nodulectomy as the preferred therapy option for late-stage podoconiosis complicated by nodules. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis (VL) is a vector-borne disease that is deadly if left untreated. Understanding which factors have prognostic value may help to focus clinical management and reduce case fatality. However, information about prognostic factors is scattered and conflicting. We conducted a systematic review and meta-analysis to identify prognostic factors for mortality among VL patients in East Africa. Methodology/Principal findings: The review protocol was registered in PROSPERO (CRD42016043112). We included studies published in English after 1970 describing VL patients treated in East African health facilities. To be included, studies had to report on associations between clinical or laboratory factors and mortality during admission or during VL treatment, with a minimal study size of ten patients. Conference abstracts and evaluations of genetic or immunological prognostic factors were excluded. We searched for studies in MEDLINE and four other databases in December 2018. To assess the risk of bias in observational studies and clinical trials, we used the Quality in Prognostic Studies (QUIPS) tool. We included 48 studies in the systematic review, describing 150,072 VL patients of whom 7,847 (5.2%) died. Twelve prognostic factors were evaluated in five or more studies and these results were submitted to meta-analysis producing one pooled crude odds ratio (OR) per prognostic factor. The following factors were strongly (OR>3) and significantly (P-value<0.05) associated with mortality: jaundice (OR = 8.27), HIV (OR = 4.60), tuberculosis (OR = 4.06), age >45 years (OR = 3.69), oedema (OR = 3.52), bleeding (OR = 3.37), and haemoglobin ≤6.5 g/dl (OR = 3.26). Factors significantly and moderately (OR between one and three) associated with death were severe malnutrition, long duration of illness, young age (<5 years), and large spleen size. Conclusions/Significance: These prognostic factors can be identified by health professionals in resource-constrained settings. They should be considered as "core" prognostic factors in future studies that aim at improving the prognosis of VL patients. Author summary: Visceral leishmaniasis (VL) is a severe disease caused by a micro-organism called Leishmania. This disease occurs in South America, East Africa, the Mediterranean, and Asia. There are several treatments with differing success rates, side effects, and costs. Some of the VL patients who seek care in health facilities die, and knowing which patients are at risk of dying is useful for patient management. Indeed, it makes sense to reserve the best treatment and closest follow-up for those patients with the highest risk of dying. We searched the medical literature in December 2018 and found 48 studies evaluating associations between clinical or laboratory factors and risk of dying among VL patients treated in East Africa. These studies described 150,072 VL patients of whom 7,847 (5.2%) died. Factors that were evaluated in five or more studies were analysed further. VL patients were at increased risk of dying if they had jaundice, HIV, tuberculosis, old (more than 45 years) or young (below five years) age, oedema, bleeding, anaemia, malnutrition, long duration of illness, and large spleen size. We recommend to include these factors, which can easily be detected by health professionals, in future studies that aim at improving the prognosis of VL patients. [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis, with 0.7 to 1.2 million cases per year globally. However, the burden of CL is poorly documented in some regions. We carried out this review to synthesize knowledge on the epidemiological burden of CL in sub-Saharan Africa. Methods: We systematically searched PubMed, CABI Global health, Africa Index Medicus databases for publications on CL and its burden. There were no restrictions on language/publication date. Case series with less than ten patients, species identification studies, reviews, non-human, and non-CL focused studies were excluded. Findings were extracted and described. The review was conducted following PRISMA guidelines; the protocol was registered in PROSPERO (42016036272). Results: From 289 identified records, 54 met eligibility criteria and were included in the synthesis. CL was reported from 13 of the 48 sub-Saharan African countries (3 eastern, nine western and one from southern Africa). More than half of the records (30/54; 56%) were from western Africa, notably Senegal, Burkina Faso and Mali. All studies were observational: 29 were descriptive case series (total 13,257 cases), and 24 followed a cross-sectional design. The majority (78%) of the studies were carried out before the year 2000. Forty-two studies mentioned the parasite species, but was either assumed or attributed on the historical account. Regional differences in clinical manifestations were reported. We found high variability across methodologies, leading to difficulties to compare or combine data. The prevalence in hospital settings among suspected cases ranged between 0.1 and 14.2%. At the community level, CL prevalence varied widely between studies. Outbreaks of thousands of cases occurred in Ethiopia, Ghana, and Sudan. Polymorphism of CL in HIV-infected people is a concern. Key information gaps in CL burden here include population-based CL prevalence/incidence, risk factors, and its socio-economic burden. Conclusion: The evidence on CL epidemiology in sub-Saharan Africa is scanty. The CL frequency and severity are poorly identified. There is a need for population-based studies to define the CL burden better. Endemic countries should consider research and action to improve burden estimation and essential control measures including diagnosis and treatment capacity. [ABSTRACT FROM AUTHOR]

Background: Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by Leishmania parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL. Methodology and principal findings: This review focuses on the frequency of TL coinfections in human populations, interactions between Leishmania and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of Trypanosoma cruzi coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., Leishmania and Sporothrix schenckii), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects. Conclusions and significance: In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL. [ABSTRACT FROM AUTHOR]

Stockouts of HIV commodities increase the risk of treatment interruption, antiretroviral resistance, treatment failure, morbidity and mortality. The study objective was to assess the magnitude and duration of stockouts of HIV medicines and diagnostic tests in public facilities in Kinshasa, Democratic Republic of the Congo. This was a cross-sectional survey involving visits to facilities and warehouses in April and May 2015. All zonal warehouses, all public facilities with more than 200 patients on antiretroviral treatment (ART) (high-burden facilities) and a purposive sample of facilities with 200 or fewer patients (low-burden facilities) in Kinshasa were selected. We focused on three adult ART formulations, cotrimoxazole tablets, and HIV diagnostic tests. Availability of items was determined by physical check, while stockout duration until the day of the survey visit was verified with stock cards. In case of ART stockouts, we asked the pharmacist in charge what the facility coping strategy was for patients needing those medicines. The study included 28 high-burden facilities and 64 low-burden facilities, together serving around 22000 ART patients. During the study period, a national shortage of the newly introduced first-line regimen Tenofovir-Lamivudine-Efavirenz resulted in stockouts of this regimen in 56% of high-burden and 43% of low-burden facilities, lasting a median of 36 (interquartile range 29–90) and 44 days (interquartile range 24–90) until the day of the survey visit, respectively. Each of the other investigated commodities were found out of stock in at least two low-burden and two high-burden facilities. In 30/41 (73%) of stockout cases, the commodity was absent at the facility but present at the upstream warehouse. In 30/57 (54%) of ART stockout cases, patients did not receive any medicines. In some cases, patients were switched to different ART formulations or regimens. Stockouts of HIV commodities were common in the visited facilities. Introduction of new ART regimens needs additional planning. [ABSTRACT FROM AUTHOR]

Background: Malaria risk can vary markedly between households in the same village, or between villages, but the determinants of this "micro-epidemiological" variation in malaria risk remain poorly understood. This study aimed to identify factors that explain fine-scale variation in malaria risk across settings and improve definitions and methods for malaria micro-epidemiology. Methods: A systematic review of studies that examined risk factors for variation in malaria infection between individuals, households, clusters, hotspots, or villages in any malaria-endemic setting was conducted. Four databases were searched for studies published up until 6th October 2015. Crude and adjusted effect estimates for risk factors for malaria infection were combined in random effects meta-analyses. Bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Results: From 743 retrieved records, 51 studies were selected, representing populations comprising over 160,000 individuals in 21 countries, in high- and low-endemicity settings. Sixty-five risk factors were identified and meta-analyses were conducted for 11 risk factors. Most studies focused on environmental factors, especially increasing distance from a breeding site (OR 0.89, 95% CI 0.86-0.92, 10 studies). Individual bed net use was protective (OR 0.63, 95% CI 0.52-0.77, 12 studies), but not household bed net ownership. Increasing household size (OR 1.08, 95% CI 1.01-1.15, 4 studies) and household crowding (OR 1.79, 95% CI 1.48-2.16, 4 studies) were associated with malaria infection. Health seeking behaviour, medical history and genetic traits were less frequently studied. Only six studies examined whether individual-level risk factors explained differences in malaria risk at village or hotspot level, and five studies reported different risk factors at different levels of analysis. The risk of bias varied from low to high in individual studies. Insufficient reporting and comparability of measurements limited the number of meta-analyses conducted. Conclusions: Several variables associated with individual-level malaria infection were identified, but there was limited evidence that these factors explain variation in malaria risk at village or hotspot level. Social, population and other factors may confound estimates of environmental risk factors, yet these variables are not included in many studies. A structured framework of malaria risk factors is proposed to improve study design and quality of evidence in future micro-epidemiological studies. [ABSTRACT FROM AUTHOR]

Human T-lymphotropic virus 1 (HTLV-1) is the etiologic agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Apoptosis is a mechanism of defense elicited by many triggers, including cross-linking of the FAS receptor expressed in viruses-infected cells, and the ligand FASL presented by T-cytotoxic cells. As HAM/TSP has been associated with high levels of proviral load (PVL), we hypothesized that certain genotypes of single-nucleotide polymorphisms (SNPs) associated with a decreased protein expression of FAS and FASL could be risk factors for this disease. Three SNPs: FAS-670A/G (rs1800682), FAS-1377G/A (rs2234767), and FASL-844C/T (rs763110) were analyzed in 73 HAM/TSP patients and 143 HTLV-1 asymptomatic carriers. Ancestry informative markers were used to adjust for ethnicity through a principal component analysis. Gender, age, PVL, and the first three principal components were used as covariates. The FAS/FASL genotype distribution was not associated with HAM/TSP presence ( P-> 0.05). The FAS-670 AA genotype was associated with high PVL in comparison to FAS-670 GG in HAM/TSP patients ( P = 0.015), while in asymptomatic carriers low levels of PVL were observed ( P > 0.05). Our findings suggest that rs1800682, rs2234767, and rs763110 genotypes are not associated with the presence of HAM/TSP, but that the FAS-670 AA genotype can promote higher PVL values in HAM/TSP patients. J. Med. Virol. 89:726-731, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article examines current standards and guidelines on writing and implementing laboratory standard operating procedures (SOP) in low-resource settings and highlights some lessons learned from a neglected infectious diseases study in the Democratic Republic of Congo. It defines SOP, cites its basic principles and highlights its significance to the practice of preventive medicine.

The article presents a case study commissioned by the Neglected Infectious Disease dIAGnosis (NIDIAG) on rapid diagnostic tests (RDT) labeling and instructions for use in persistent fever, with emphasis on in vitro diagnostic tests (IVD). It highlights the need for proactive interest from IVD manufacturers in connection with ISO 13485 guidelines.

In resource-limited settings, the scarcity of skilled personnel and adequate laboratory facilities makes the differential diagnosis of fevers complex [–]. Febrile illnesses are diagnosed clinically in most rural centers, and both Rapid Diagnostic Tests (RDTs) and clinical algorithms can be valuable aids to health workers and facilitate therapeutic decisions [,]. The persistent fever syndrome targeted by NIDIAG is defined as presence of fever for at least one week. The NIDIAG clinical research consortium focused on potentially severe and treatable infections and therefore targeted the following conditions as differential diagnosis of persistent fever: visceral leishmaniasis (VL), human African trypanosomiasis (HAT), enteric (typhoid and paratyphoid) fever, brucellosis, melioidosis, leptospirosis, malaria, tuberculosis, amoebic liver abscess, relapsing fever, HIV/AIDS, rickettsiosis, and other infectious diseases (e.g., pneumonia). From January 2013 to October 2014, a prospective clinical phase III diagnostic accuracy study was conducted in one site in Cambodia, two sites in Nepal, two sites in Democratic Republic of the Congo (DRC), and one site in Sudan (clinicaltrials.gov no. NCT01766830). The study objectives were to (1) determine the prevalence of the target diseases in patients presenting with persistent fever, (2) assess the predictive value of clinical and first-line laboratory features, and (3) assess the diagnostic accuracy of several RDTs for the diagnosis of the different target conditions. [ABSTRACT FROM AUTHOR]

Human T-lymphotropic virus 1 (HTLV-1) is a retrovirus that produces a persistent infection. Two transmission routes (from mother to child and via sexual intercourse) favor familial clustering of HTLV-1. It is yet unknown why most HTLV-1 carriers remain asymptomatic while about 10% of them develop complications. HTLV-1 associated diseases were originally described as sporadic entities, but familial presentations have been reported. To explore what is known about family aggregation of HTLV-1-associated diseases we undertook a systematic review. We aimed at answering whether, when, and where family aggregation of HTLV-1-associated diseases was reported, which relatives were affected and which hypotheses were proposed to explain aggregation. We searched MEDLINE, abstract books of HTLV conferences and reference lists of selected papers. Search terms used referred to HTLV-1 infection, and HTLV-1-associated diseases, and family studies. HTLV-1-associated diseases considered are adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-1-associated uveitis, and infective dermatitis. Seventy-four records reported HTLV-1-associated diseases in more than one member of the same family and were included. Most reports came from HTLV-1-endemic countries, mainly Japan (n = 30) and Brazil (n = 10). These reports described a total of 270 families in which more than one relative had HTLV-1-associated diseases. In most families, different family members suffered from the same disease (n = 223). The diseases most frequently reported were ATLL (115 families) and HAM/TSP (102 families). Most families (n = 144) included two to four affected individuals. The proportion of ATLL patients with family history of ATLL ranged from 2 to 26%. The proportion of HAM/TSP patients with family history of HAM/TSP ranged from 1 to 48%. The predominant cluster types for ATLL were clusters of siblings and parent-child pairs and for HAM/TSP, an affected parent with one or more affected children. The evidence in the literature, although weak, does suggest that HTLV-1-associated diseases sometimes cluster in families. Whether familial transmission of HTLV-1 is the only determining factor, or whether other factors are also involved, needs further research. [ABSTRACT FROM AUTHOR]

Background: Household contacts (HHCs) of TB cases are at increased risk for TB disease compared to the general population but the risk may be modified by individual or household factors. We conducted a study to determine incident TB among HHCs over two years after exposure and to identify individual and household level risk factors.Methods: Adults newly diagnosed with a first episode of smear-positive pulmonary TB (index cases) between March 2010 and December 2011 in eastern Lima, were interviewed to identify their HHC and household characteristics. TB registers were reviewed for up to two years after the index case diagnosis and house visits were made to ascertain TB cases among HHC. The TB incidence rate ratio among HHCs as a function of risk factors was determined using generalized linear mixed models.Results: The 1178 index cases reported 5466 HHCs. In 402/1178 (34.1 %) households, at least one HHC had experienced a TB episode ever. The TB incidence among HHCs was 1918 (95%CI 1669-2194) per 100,000 person-years overall, and was 2392 (95%CI 2005-2833) and 1435 (95%CI 1139-1787) per 100,000 person-years in the first and second year, respectively. Incident TB occurred more than six months following the index case's TB diagnosis in 121/205 (59.0 %) HHCs. In HHCs, bacillary load and time between symptoms and treatment initiation in the index case, as well as the relationship to the index case and the sex of the HHC all had a significant association with TB incidence in HHCs.Conclusions: Incidence of TB among HHCs was more than ten times higher than in the general population. Certain HHC and households were at higher risk of TB, we recommend studies to compare HHC investigation to households at highest risk versus current practice, in terms of efficiency. [ABSTRACT FROM AUTHOR]

Objective. To measure time between onset of tuberculosis (TB) symptoms and start of treatment, and to identify factors associated with delay in eight Colombian cities. Methods. Operational research with a retrospective analytical cohort design was conducted in 2014 using routinely collected data about new smear-positive pulmonary TB patients from eight cities in Colombia (Barranquilla, Bogotá, Bucaramanga, Cali, Cúcuta, Medellín, Pereira, and Villavicencio). Date of symptom onset was sourced from TB surveillance databases. Data on all other variables came from National TB Program (NTP) registers. Results. There were 2 545 new cases of smear-positive pulmonary TB, but a plausible date of symptom onset was available for only 1 456 (57%). Median number of days between symptom onset and treatment start was 51 days (interquartile range: 27-101). A total of 72% of patients had a delay (> 30 days between symptom onset and treatment start), and 28% had a 3+ bacillary load at diagnosis. Based on multiple logistic regression, three factors were significantly associated with delay: being uninsured (odds ratio (OR): 1.30; 95% confidence interval (CI): 1.01-1.68) and having an unknown HIV status (OR: 1.81; CI: 1.04-3.17), which increased risk, and coming from a neighborhood with NTP-employed community health workers, which decreased risk (OR: 0.56; CI: 0.34-0.90). Conclusions. Delays still prevent timely TB diagnosis and treatment in Colombia. As the country aims for TB elimination, delays must be reduced, especially in cities and vulnerable neighborhoods, to stop community transmission. The NTP should focus not only on the number of cases detected but also on how long it takes to detect them. To monitor interventions designed to reduce delays, additional dates in the process should be recorded routinely. In addition, reliability and completeness of data are crucial for monitoring. . [ABSTRACT FROM AUTHOR]

Background: Cancer of the uterine cervix is the leading cause of cancer-related death among women in Sub-Saharan Africa, but information from the Democratic Republic of the Congo (DRC) is scarce. The study objectives were to: 1/ assess prevalence of (pre)cancerous cervical lesions in adult women in Kinshasa, 2/ identify associated sociodemographic and behavioural factors and 3/ describe human papillomavirus (HPV) types in cervical lesions. Methods: A cross-sectional study was conducted in Kinshasa. Between 2006 and 2013, four groups of women were recruited. The first two groups were included at HIV screening centres. Group 1 consisted of HIV-positive and group 2 of HIV-negative women. Group 3 was included in large hospitals and group 4 in primary health centres. Pap smears were studied by monolayer technique (Bethesda classification). Low- or high-grade squamous intraepithelial lesions or carcinoma were classified as LSIL+. HPV types were determined by INNO-LiPA®. Bivariate and multivariable analyses (logistic regression and generalised estimating equations (GEE)) were used to assess associations between explanatory variables and LSIL+. Results: LSIL+ lesions were found in 76 out of 1018 participants. The prevalence was 31.3 % in group 1 (n = 131 HIV-positive women), 3.9 % in group 2 (n = 128 HIV-negative women), 3.9 % in group 3 (n = 539) and 4.1 % in group 4 (n = 220). The following variables were included in the GEE model but did not reach statistical significance: history of abortion, ≥3 sexual partners and use of chemical products for vaginal care. In groups 3 and 4 where this information was available, the use of plants for vaginal care was associated with LSIL+ (adjusted OR 2.70 (95 % confidence interval 1.04 - 7.01). The most common HPV types among HIV-positive women with ASCUS+ cytology (ASCUS or worse) were HPV68 (12 out of 50 samples tested), HPV35 (12/50), HPV52 (12/50) and HPV16 (10/50). Among women with negative/unknown HIV status, the most common types were HPV52 (10/40), HPV35, (6/40) and HPV18 (5/40). Conclusion: LSIL+ lesions are frequent among women in Kinshasa. The use of plants for vaginal care deserves attention as a possible risk factor for LSIL+. In this setting, HPV16 is not the most frequent genotype in samples of LSIL+ lesions. [ABSTRACT FROM AUTHOR]

Background Cervical cancer is the most frequent cancer of women in the Democratic Republic of Congo (DRC). Nevertheless, the level of women's awareness about cervical cancer is unknown. Knowledge, attitude and practice (KAP) are important elements for designing and monitoring screening programs. The study purpose was to estimate KAP on cervical cancer and to identify associated factors. Methods A cross-sectional study was conducted in Kinshasa, DRC, including 524 women aged 16-78 years (median age 28; interquartile range 22-35). The women were interviewed at home by trained field workers using a standardized questionnaire. The women's score on knowledge, attitude and practice were dichotomized as sufficient or insufficient. We used binary and multiple logistic regression to assess associations between obtaining sufficient scores and a series of socio-demographic factors: age, residence, marital status, education, occupation, religion, and parity. Results The women's score on knowledge was not significantly correlated with their score on practice (Spearman's rho = 0.08; P > 0.05). Obtaining a sufficient score on knowledge was positively associated with higher education (adjusted odds ratio (OR) 7.65; 95% confidence interval (95%CI) 3.31-17.66) and formal employment (adjusted OR 3.35; 95%CI 1.85-6.09); it was negatively associated with being single (adjusted OR 0.44; 95%CI 0.24-0.81) and living in the eastern, western and northern zone of Kinshasa compared to the city centre. The attitude score was associated with place of residence (adjusted OR for east Kinshasa: 0.49; 95%CI 0.27-0.86 and for south Kinshasa: 0.48; 95%CI 0.27-0.85) and with religion (adjusted OR 0.55; 95%CI 0.35-0.86 for women with a religion other than Catholicism or Protestantism compared to Catholics). Regarding practice, there were negative associations between a sufficient score on practice and being single (adjusted OR 0.24; 95%CI 0.13-0.41) and living in the eastern zone of the city (adjusted OR 0.39; 95%CI 0.22-0.70). Although 84% of women had heard about cervical cancer, only 9% had ever had a Papanicolaou (Pap) smear test. Conclusions This study shows a low level of knowledge, attitude and practice on cervical cancer among women in Kinshasa. Increasing women's awareness would be a first step in the long chain of conditions to attain a lower incidence and mortality. [ABSTRACT FROM AUTHOR]

Impoverished populations carry a disproportionately high share of the burden of neglected tropical diseases, including dengue. The burden of dengue is high among poor people because they often live in communities where mosquito vectors are abundant, because they use less vector-human barrier methods, and because interventions tend to be less effective in disadvantaged populations. We believe that a better understanding and management of the "causes behind the causes" of dengue would lead to more equitable and more effective control strategies. Two main ideas are worked out. First, we propose targeted interventions in well-defined geographical areas with high risk of dengue transmission. The definition of these high-risk areas should be based on socio-economical, entomological, environmental as well as epidemiological information. Second, there is a need to adapt dengue control tools to local, context-specific factors, in active collaboration with the sectors involved in risk management as well as with the affected communities. [ABSTRACT FROM AUTHOR]

Human T-lymphotropic Virus-1 (HTLV-1) is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH), appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone). A newly developed biodiversity estimator called "DivE" was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance) of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1+ T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1+ clones. [ABSTRACT FROM AUTHOR]

Background: Human strongyloidiasis varies from a chronic but limited infection in normal hosts to hyperinfection in patients treated with corticosteroids or with HTLV-1 co-infection. Regulatory T cells dampen immune responses to infections. How human strongyloidiasis is controlled and how HTLV-1 infection affects this control are not clear. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis infection by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite. Objective: To measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from newly diagnosed strongyloidiasis patients with or without HTLV-1 co-infection. Regulatory T cells were characterized by flow cytometry using intracellular staining for CD4, CD25 and FoxP3. PBMCs were also cultured with and without Strongyloides larval antigens. Supernatants were analyzed for IL-5 production. Results: Patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens. Eosinophil counts were decreased in the HTLV-1 and Strongyloides co-infected subjects compared to strongyloidiasis-only patients (70.0 vs. 502.5 cells/mm3, p = 0.09, Mann-Whitney test). The proportion of regulatory T cells was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis or asymptomatic HTLV-1 carriers (median = 17.9% vs. 4.3% vs. 5.9 p<0.05, One-way ANOVA). Strongyloides antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients (5.0 vs. 187.5 pg/ml, p = 0.03, Mann-Whitney test). Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of CD4+CD25+FoxP3+ cells. Conclusions: Regulatory T cell counts are increased in patients with HTLV-1 and Strongyloides stercoralis co-infection and correlate with both low circulating eosinophil counts and reduced antigen-driven IL-5 production. These findings suggest a role for regulatory T cells in susceptibility to Strongyloides hyperinfection. Author Summary: Human strongyloidiasis varies from a mild, controlled infection to a severe frequently fatal disseminated infection depending on the hosts. Patients infected with the retrovirus HTLV-1 have more frequent and more severe forms of strongyloidiasis. It is not clear how human strongyloidiasis is controlled by the immune system and how HTLV-1 infection affects this control. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite. In our study, patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens than patients with only strongyloidiasis. Eosinophils play an essential role in control of strongyloidiasis in animal models, and eosinophil counts were decreased in the HTLV-1 and Strongyloides stercoralis co-infected subjects compared to patients with only strongyloidiasis. The proportion of T cells with a regulatory cell phenotype was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis. IL-5 is a key host molecule in stimulating eosinophil production and activation, and Strongyloides stercoralis antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients. Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of regulatory T cells. These findings suggest a role for regulatory T cells in susceptibility to Strongyloides hyperinfection. [ABSTRACT FROM AUTHOR]

Background: Cuzco, a Peruvian city of historical interest located 3,326 m above sea level, is a frequent destination for tourists. We conducted a descriptive study to assess the extent and sources of pretravel health advice received by international travelers before their arrival to Cuzco.Methods: Data were collected as part of a health survey among travelers. Between August and November 2002, travelers between 15 and 65 years old were invited to fill out a questionnaire in the departing area of Cuzco's international airport.Results: A total of 5,988 travelers participated. The mean age was 35.4 years (SD 11.4 yr); 50.6% were female and 50.8% were single. Tourism was the reason for traveling in 90.2% of the participants, and 89.3% of them were traveling with companions. Pretravel health information was received by 93.6%. The median number of information sources was two, with books (41.5%), travel medicine clinics (38.8%), the Internet (23.3%), and general practitioners (22.7%) as the main sources. Most frequently received recommendations were about safe food and water consumption (85%), use of insect repellents (66.0%), sunburn protection (64.4%), and condom use (22%). Only 16.5% took medication to prevent altitude sickness, and 14.2% took medication to prevent traveler's diarrhea. Variables independently associated with receiving pretravel health information from a health care professional were female gender, country of residence other than the United States, length of stay in Cuzco > 7 days, length of stay in other Peruvian cities > 7 days, tourism as the main reason for visiting Cuzco, traveling with companions, and consulting of more than one source of information.Conclusions: Most travelers arriving to Cuzco had received pretravel health information, and the majority obtained it from more than one source. Recommendations addressed for specific health risks, such as altitude sickness prophylaxis, were received by few travelers. [ABSTRACT FROM AUTHOR]