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BACKGROUND: This study assesses the impact of the Xpert MTB/RIF in the diagnosis of childhood tuberculosis (TB) in a rural hospital in a resource-constrained setting. METHODS: Retrospective cross-sectional study in children evaluated for presumptive TB from 1 June 2016 to 31 May 2017 at the Gambo General Hospital in rural Southern Ethiopia. Children were evaluated according to a defined protocol based on national guidelines. Samples were submitted for Xpert MTB/RIF assay to the nearest reference laboratory. RESULTS: Of the 201 children assessed for presumptive TB, 46.3% (93/201) were diagnosed with TB. Of these, 49.5% (46/93) were microbiologically confirmed, mostly by Xpert MTB/RIF (only one patient was diagnosed by smear alone). The rest were clinically diagnosed. Microbiologically confirmed patients had a higher mean age, longer duration of fever and cough and lymphadenopathy more frequently than those clinically diagnosed. Gastric aspirates were Xpert MTB/RIF-positive in 18.2% of the samples (26/143); none were smear-positive (0/140). Sputum samples were Xpert MTB/RIF-positive in 27.1% (13/35) of the samples and smear-positive in 8.6% (3/35). There were no HIV-positive patients and just one case of rifampicin-resistant TB. A long delay (median 15 days) was detected in returning the results. CONCLUSION: Xpert MTB/RIF serves as an important adjunctive test for diagnosing childhood TB in rural settings, with microbiological confirmation in up to half the TB cases. Processes need to be optimized to achieve an early diagnosis. The diagnosis of childhood TB in high-burden countries such as Ethiopia still relies largely upon diagnostic algorithms and the clinician's skills.Lay summaryWorld Health Organization recommends the use of Xpert MTB/RIF to improve the microbiological diagnosis of childhood tuberculosis (TB) since 2014, but the impact of this test under real conditions in rural areas of low-income countries is not clear. We conducted a cross-sectional study in children evaluated for presumptive TB from 1 June 2016 to 31 May 2017 at the Gambo General Hospital in rural Southern Ethiopia. Children were evaluated according to a clinical protocol based on national guidelines and samples were submitted for Xpert MTB/RIF assay to the nearest reference laboratory.Of the 201 children assessed, 46.3% (93/201) were diagnosed with tuberculosis. Of these, 48.4% (45/93) were microbiologically confirmed by Xpert MTB/RIF [smear microscopy only diagnosed the 5.4% (5/93)]. Patients with microbiologically confirmed tuberculosis had a higher mean age, longer duration of fever and cough and had lymphadenopathy more frequently than those clinically diagnosed. A long delay in returning the results (median 15 days) was detected. Xpert MTB/RIF serves as an important test for diagnosing childhood TB in rural settings, with microbiological confirmation in up to half the cases. Processes need to be optimized to achieve an early diagnosis. The diagnosis of childhood TB in high-burden countries still relies largely upon diagnostic algorithms and the clinician's skills.

Background: HIV-2 is a neglected virus despite estimates of 1–2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with inte- grase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modal- ities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. Results: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). Conclusions: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individ- uals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

There are few data available about childhood tuberculosis (TB) in rural hospitals in low-income countries. We assessed differences in epidemiological characteristics and treatment outcomes in children with TB aged 0-4 versus 5-14 years in rural Ethiopia.

Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism is related to CD4 + recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential impact in patients with very low CD4 + T-cells count. We aimed to analyze the association between IL7RA rs6897932 polymorphism and CD4 + T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4 + T-cells count 200 cells/mm 3 . We performed a retrospective study in 411 patients followed for 24 months with a DNA sample available for genotyping. The change in CD4 + T-cells count during the follow-up was considered as the primary outcome. The rs6897932 polymorphism had a minimum allele frequency (MAF) 20% and was in Hardy-Weinberg equilibrium ( p = 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4 + T-cells recovery (arithmetic mean ratio; AMR = 1.16; p = 0.016), higher CD4 + T-cells increase (AMR = 1.19; p = 0.004), and higher CD4 + T-cells count at the end of follow-up (AMR = 1.13; p = 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4 + T-cells at the end of follow-up =500 CD4 + cells/mm 3 (OR = 2.44; p = 0.006). After multiple testing correction (Benjamini-Hochberg), only the increase of = 400 CD4 + cells/mm 3 lost statistical significance ( p = 0.052). IL7RA rs6897932 CT/TT genotype was related to a better CD4 + T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4 + T-cells count 200 cells/mm 3 .

Not all HIV-infected patients receiving cART are able to recover optimal CD4-T cell levels despite achieving undetectable viremia. We evaluated the potential association between polymorphisms (SNPs) in cytokines involved in immune response (IL15, IFN gamma and IL19) and the failure to achieve optimal CD4 T-cells restoration after cART. For this, we carried out a retrospective study in 412 HIV-infected patients starting cART with CD4 < 200 cells/mu L. These patients were classified as immunological non-responders (INR) if having a CD4 increase (Delta CD4) below 200 cells/mu L after two years on successful cART. IL15, IFN gamma and IL19 polymorphisms were genotyped using Sequenom's MassARRAY platform. We found 134 INR patients with a median [IQR] Delta CD4 = 133[73-174] cells/mu L. In the multivariate analysis adjusted for age, sex, infection route, ethnic origin, hepatitis co-infection and HIV infection length, the AA genotype of the SNP rs2430561 in IFN gamma (OR:2.01[1.13-3.56], p=0.017) and the TT genotype of polymorphism rs2243191 in IL19 (OR:2.58 [1.17-5.68], p=0.019) showed significant association with the INR status. Our results show that polymorphisms in IFN gamma and IL19 genes significantly impacts in the probability of not achieving an optimal immune recovery in HIV-patients starting cART with CD4 T-cells < 200 cells/mu L. Thus, these SNPs could represent potential predictive markers of the immunodiscordant response.

Not all HIV-infected patients receiving cART are able to recover optimal CD4-T cell levels despite achieving undetectable viremia. We evaluated the potential association between polymorphisms (SNPs) in cytokines involved in immune response (IL15, IFN? and IL19) and the failure to achieve optimal CD4 T-cells restoration after cART. For this, we carried out a retrospective study in 412 HIV-infected patients starting cART with CD4

Bacterial arthropod-borne pathogens are a common cause of fever in Africa, but their precise impact is unknown and usually underdiagnosed in the basic rural laboratories of low-resourced African countries. Our aim was to determine the prevalence of arthropod-borne bacterial diseases causing fever among malaria smear-negative patients in a rural hospital located in Ethiopia. The study population included patients aged 2 years or older; referred to Gambo Rural General Hospital (West Arsi, Ethiopia), between July and November 2013, for fever or report of fever in the previous 48 h; attending the outpatient department; and testing negative for malaria by Giemsa-stained thin blood smears. We extracted DNA from 394 whole blood samples, using reverse line blot assays of amplicons to look for bacteria from the genera: Anaplasma , Bartonella , Borrelia , Coxiella , Ehrlichia , Francisella , and Rickettsia . Thirteen patients showed presence of DNA for these pathogens: three each by Borrelia spp., the Francisella group ( F. tularensis tularensis , F. tularensis holartica , and F. novicia) , Rickettsia bellii , and Rickettsia Felis , and one by Bartonella rochalimae . Thus, in this rural area of Africa, febrile symptoms could be due to bacteria transmitted by arthropods. Further studies are needed to evaluate the pathogenic role of R. bellii .

Objective We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts. Methods A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count

Evolution of incident malaria and frequency of anemia were analyzed over eight years in a rural hospital in southern Ethiopia. Capillary blood samples were tested for hemoglobin concentration, and in some instances for malaria parasites, at Gambo Rural General Hospital between January 2007 and September 2014, and the results recorded. Main demographic data were also recorded in subjects with Plasmodium sp. infections. Of a total of 54,493 blood samples taken from 45,096 different patients, 21,723 (39.9%) samples from 19,173 (42.5%) patients were tested for malaria parasites. Malaria was diagnosed in 825 (3.79%, 95% CI 3.55%, 4.06%) instances (58.3% P. vivax and 41.7% P. falciparum; one episode in 575 patients and two episodes in 125 patients). A sustained decrease in yearly incidence of malaria was observed between 2011 (6.1%) and 2014 (2.4%) (p

INTRODUCTION: Cutaneous anthrax is a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, which typically presents with ulcers after contact with animals or animal products, and is rarely seen in high-income countries but is common in those with low- and middle-incomes. Objective. The aim of this study is to show the main clinical characteristics of cutaneous anthrax in endemic areas. MATERIAL AND METHODS: The study describes the main clinical characteristics of cutaneous anthrax in eight patients (six female and two male, age range 1 - 56 years) admitted to the rural General Hospital of Gambo, West Arsi Province of Ethiopia from 2010-2013. RESULTS: In all cases, lesions began as an erythematous papule located on exposed sites (n=7 head; n=1 thigh) and subsequently became a necrotic black eschar surrounded by an edematous halo. Two patients presented with painful ipsilateral adenopathy near the black eschar. Four patients developed a malignant pustule on the suborbital region of the face. Patients responded positively to treatment, and the lesions resolved, leaving eschars. However, one patient suffered the loss of an eyeball, and another died 12 hours after starting treatment. CONCLUSIONS: Physicians working in rural areas of resource-poor settings should be trained in the clinical identification of cutaneous anthrax. Early antibiotic treatment is essential for decreasing morbidity and mortality.

HIV-2 and HTLV-1 infections are globally less frequent than those produced by HIV-1, the classical AIDS agent. In Spain and up to the end of 2014, a total of 310 cases of HIV-2, 274 of HTLV-1, and 776 of HTLV-2 infections had been reported. No cases of HTLV-3 or HTLV-4 infections have been identified so far in Spain. Most persons infected with HIV-2 or HTLV-1 acknowledge epidemiological risk factors for contagion, such as originating from or living in endemic regions and/or having had sexual partners from those areas. However, risk factors could not be recognized in up to 20-25% of carriers in Spain. Thus, it seems worth keeping a high level of clinical suspicion in order to identify earlier these neglected human retroviral infections, since diagnostic procedures and antiviral treatment are specific for each of these agents. In this article we summarize the major contributions reported at the meeting of the Spanish Group for HIV-2/HTLV held in Madrid in December 2014

Histoplasmosis is an endemic mycosis of the Americas, Africa, and Asia. In Spain, it is the most common imported endemic mycosis appearing in the literature, and its incidence is on the rise. Proper differential diagnosis of the disease must be taken into consideration by otorhinolaryngologists, as the clinical manifestations of histoplasmosis may simulate more prevalent diseases such as cancer or tuberculosis. We present the case of a Spanish patient with focal involvement of the larynx and offer a review of the relevant literature.

Leishmania infection may be associated with immunecomplex-mediated glomerular injury. Contrary to immune-competent individuals, leishmaniasis in HIV patients is a chronic, relapsing disease. Despite the increasing frequency of the Leishmania/ HIV co-infection, there is a paucity of information on the effects of such co-infection in the kidney. We present a patient with AIDS and refractory, relapsing visceral leishmaniasis who developed nephrotic syndrome associated with renal involvement by Leishmania in the absence ofimmunecomplex glomerular deposition. For the first time, the relapsing nature of renal injury in this context is documented.

The characteristics of two cases of histoplasmosis in AIDS patients in our institution are presented together with a review of the 11 cases published in Spain since 1988 in addition to the current knowledge on histoplasmosis in patients with human immunodeficiency virus infection (HIV). In all except 2 of the 13 patients there was epidemiologic history of a stay in a country in which histoplasmosis is endemic. The 12 cases described in which this information is available had CD4 counts under 100/microL. The clinical manifestations of presentation were fever (92.3%) associated or not with other unspecific symptoms (asthenia, anorexia, cough, diarrhea) with a subacute course of two or three months. Physical examination demonstrated hepatosplenomegaly in 76.9% of the cases and 61.5% of the patients presented cutaneous lesions. Thoracic radiography was abnormal in 55% (61.5% had respiratory symptoms). Diagnosis was achieved by isolation of the fungus in the cutaneous biopsies in all the patients with dermatologic involvement and in 7 cases identification was performed in the bone marrow. In all the cases induction treatment was with anphotericin B and in those who reached the maintenance phase itraconazol was used in 7 cases and ketoconazol in one case. None of the patients treated with itraconazol, including the two in our center, presented recurrence at the time of completion of follow up. In conclusion, histoplasmosis is frequently presented as a prolonged febrile syndrome with unspecific characteristics, thus emphasizing the importance of including travel history to other countries in the anamnesis. The increase in journeys to endemic countries and immigration from these areas had led to an increase in the number of cases of histoplasmosis in patients with HIV infection in Spain.