Search

Guatemala is a developing country in Central America with a high burden of HIV and endemic fungal infections; we attempted to estimate the burden of serious fungal infections for the country. A full literature search was done to identify epidemiology papers reporting fungal infections from Guatemala. We used specific populations at risk and fungal infection frequencies in the population to estimate national rates. The population of Guatemala in 2013 was 15.4 million; 40% were younger than 15 and 6.2% older than 60. There are an estimated 53,000 adults with HIV infection, in 2015, most presenting late. The estimated cases of opportunistic fungal infections were: 705 cases of disseminated histoplasmosis, 408 cases of cryptococcal meningitis, 816 cases of Pneumocystis pneumonia, 16,695 cases of oral candidiasis, and 4,505 cases of esophageal candidiasis. In the general population, an estimated 5,568 adult asthmatics have allergic bronchopulmonary aspergillosis (ABPA) based on a 2.42% prevalence of asthma and a 2.5% ABPA proportion. Amongst 2,452 pulmonary tuberculosis patients, we estimated a prevalence of 495 for chronic pulmonary aspergillosis in this group, and 1,484 for all conditions. An estimated 232,357 cases of recurrent vulvovaginal candidiasis is likely. Overall, 1.7% of the population are affected by these conditions. The true fungal infection burden in Guatemala is unknown. Tools and training for improved diagnosis are needed. Additional research on prevalence is needed to employ public health measures towards treatment and improving the reported data of fungal diseases. [ABSTRACT FROM AUTHOR]

Background A Diagnostic Laboratory Hub (DLH) was set up in Guatemala to provide opportunistic infection (OI) diagnosis for people with HIV (PWH). Methods Patients newly presenting for HIV, PWH not receiving antiretrovirals (ARVs) for >90 days but returned to care (Return/Restart), and PWH on ARVs with symptoms of OIs (ARV treatment) were prospectively included. Screening for tuberculosis, nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcosis was done. Samples were couriered to the DLH, and results were transmitted electronically. Demographic, diagnostic results, disease burden, treatment, and follow-up to 180 days were analyzed. Results In 2017, 1953 patients were included, 923 new HIV infections (an estimated 44% of all new HIV infections in Guatemala), 701 on ARV treatment, and 315 Return/Restart. Three hundred seventeen (16.2%) had an OI: 35.9% tuberculosis, 31.2% histoplasmosis, 18.6% cryptococcosis, 4.4% NTM, and 9.8% coinfections. Histoplasmosis was the most frequent AIDS-defining illness; 51.2% of new patients had <200 CD4 cells/mm3 with a 29.4% OI incidence; 14.3% of OIs in new HIV infections occurred with CD4 counts of 200–350 cells/mm3. OIs were the main risk factor for premature death for new HIV infections. At 180 days, patients with OIs and advanced HIV had 73-fold greater risk of death than those without advanced disease who were OI-free. Conclusions The DLH OI screening approach provides adequate diagnostic services and obtains relevant data. We propose a CD4 screening threshold of <350 cells/mm3. Mortality remains high, and improved interventions are required, including expansion of the DLH and access to antifungal drugs, especially liposomal amphotericin B and flucytosine. [ABSTRACT FROM AUTHOR]

Abstract Background Violence against women by their male intimate partners (IPV) during pregnancy may lead to negative pregnancy outcomes. We examined the role of IPV as a potential risk factor for miscarriage in Guatemala. Our objectives were: (1) To describe the magnitude and pattern of verbal, physical and sexual violence by male intimate partners in the last 12 months (IPV) in a sample of pregnant Guatemalans; (2) To evaluate the influence of physical or sexual IPV on miscarriage as a pregnancy outcome. Methods All pregnant women reporting to the maternity of a major tertiary care public hospital in Guatemala City from June 1st to September 30th, 2006 were invited to participate in this cross-sectional study. The admitting physician assessed occurrence of miscarriage, defined as involuntary pregnancy loss up to and including 28 weeks gestation. Data on IPV, social and demographic characteristics, risk behaviours, and medical history were collected by interviewer-administered questionnaire. Laboratory testing was performed for HIV and syphilis. The relationship between IPV and miscarriage was assessed through multivariable logistic regression. Results IPV affected 18% of the 1897 pregnant Guatemalan women aged 15-47 in this sample. Verbal IPV was most common (16%), followed by physical (10%) and sexual (3%) victimisation. Different forms of IPV were often co-prevalent. Miscarriage was experienced by 10% of the sample (n = 190). After adjustment for potentially confounding factors, physical or sexual victimisation by a male intimate partner in the last 12 months was significantly associated with miscarriage (ORadj 1.1 to 2.8). Results were robust under a range of analytic assumptions. Conclusions Physical and sexual IPV is associated with miscarriage in this Guatemalan facility-based sample. Results cohere well with findings from population-based surveys. IPV should be recognised as a potential cause of miscarriage. Reproductive health services should be used to screen for spousal violence and link to assistance.

Background: In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections., Methods: This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala., Results: Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20 cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6 months of baseline evaluation, for a mortality rate of 57.1%., Conclusions: PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The absence of awareness of fungal diseases as part of the differential diagnosis in at-risk populations has severe consequences. Here, we show how the active role of laboratories can improve patients’ survival. Recently, major advances have been made in non-culture-based assays for fungal diseases, improving accuracy and turnaround time. Furthermore, with the introduction of proficiency control systems, laboratories are an easily monitored environment with good analytical accuracy. Diagnostic packages for opportunistic infections can overcome many deficiencies caused by the absence of awareness. In Guatemala, to make diagnosis accessible, we set up a diagnostic laboratory hub (DLH) providing screening for cryptococcosis, histoplasmosis and tuberculosis to a network of 13 healthcare facilities attending people living with HIV (PLWHIV). In two years, we screened 2127 newly HIV-diagnosed patients. The frequency of opportunistic infections was 21%, rising to 30.3% in patients with advanced HIV disease (<200 CD4); 8.1% of these patients had more than one infection. With the implementation of this diagnostic package, mortality decreased by 7%, a key goal of many public health interventions. Screening for serious infection in high-risk populations can partially overcome training or experiential deficiencies among clinicians for life-threatening fungal diseases.

Background: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem., Objectives: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA)., Methods: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done., Results: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)-β-d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal., Conclusions: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed., (© 2022 The Authors. Mycoses published by Wiley-VCH GmbH.)

Cryptococcal disease is an important opportunistic infection among people living with HIV. The cryptococcal antigen (CrAg) can be detected before the clinical onset of meningitis and its screening is recommended. Here, we evaluated CrAg frequency, and describe the epidemiological characteristics and mortality at 180 days in a cohort of HIV patients from Guatemala. A total of 3457 patients were screened with a CrAg lateral flow assay in serum between January 2017 and December 2018. CrAg positivity was 11.5% in patients with ≤100 CD4/mm3, 8.7% in patients with <200 CD4/mm3, and 6.3% in patients with <350 CD4/mm3. In Latin America, we estimated 9.2% CrAg positivity (IC95% 7.9−10.7%) in patients with ≤100 CD4/mm3. Among patients newly diagnosed with HIV, we estimated 4416 incident cases per year in Latin America in those with <200 CD4/mm3 and 5289 in those with <350 CD4/mm3. In addition, we calculated the burden in people not on ARV or without viral suppression and found 28,672 cases. CrAg screening should be considered in patients who have a CD4 cell count < 350 cells/mm3. Cryptococcal meningitis was associated with 30.8% mortality in Guatemala. Global access to diagnosis as well as to liposomal amphotericin B and flucytosine is a priority.

There is little information about the amount of recent tuberculosis transmission in low-income settings. Genetic clustering can help identify ongoing transmission events. A retrospective observational study was performed on Mycobacterium tuberculosis isolates from persons living with HIV (PLHIV) and HIV-seronegative participants who submitted samples to a referral tuberculosis laboratory in Guatemala City, Guatemala from 2010 to 2014. Genotyping results were classified according to the international spoligotyping database, SITVIT2. Spoligotype patterns were categorized as clustered or nonclustered depending on their genotype. The proportion of clustering and the index of recent transmission index (RTIn-1) were estimated. In the RTIn-1 method, clustered cases represent recent transmission, whereas nonclustered cases represent reactivation of older tuberculosis infections. As a secondary aim, the potential risk factors associated with clustering in isolates from the subset of participants living with HIV were explored. From 2010 to 2014, a total of 479 study participants were confirmed as culture-positive tuberculosis cases. Among the 400 available isolates, 71 spoligotype patterns were identified. Overall, the most frequent spoligotyping families were Latin American-Mediterranean (LAM) (39%), followed by T (22%) and Haarlem (14%). Out of the 400 isolates, 365 were grouped in 36 clusters (range of cluster size: 2-92). Thus, the proportion of clustering was 91% and the RTIn-1 was 82%. Among PLHIV, pulmonary tuberculosis was associated with clustering (OR = 4.3, 95% CI 1.0-17.7). Our findings suggest high levels of ongoing transmission of M. tuberculosis in Guatemala as revealed by the high proportion of isolates falling into genomic clusters.

Among people with HIV, histoplasmosis represents an important cause of mortality. Previous studies provided estimates of the disease incidence. Here, we compared those estimates with the results obtained from a screening program implemented in Guatemala, which included histoplasmosis detection for people with HIV. To compare the results of this program with previous estimations, a literature search was performed and reports concerning histoplasmosis incidence were analyzed. The screening program enrolled 6366 patients. The overall histoplasmosis incidence in the screening program was 7.4%, which was almost double that estimated in previous studies. From 2017 to 2019, the screening program showed an upward trend in histoplasmosis cases from 6.5% to 8.8%. Histoplasmosis overall mortality among those who were newly HIV diagnosed showed a decrease at 180 days from 32.8% in 2017 to 21.2% in 2019. The screening approach using rapid diagnostic assays detects histoplasmosis cases more quickly, allowing a specific treatment to be administered, which decreases the mortality of the disease. Therefore, the use of these new techniques, especially in endemic areas of histoplasmosis, must be implemented.

Objectives: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory tests, such as culture and microscopy, are not optimal; however, antigen (Ag) tests are rapid, highly sensitive, and specific for diagnosis of fungal opportunistic infections (OI). The aim of this study was to describe the results of a laboratory-based surveillance system for histoplasmosis and cryptococcosis., Methods: An observational cross-sectional study based on laboratory surveillance, was carried out in two hospitals in Guatemala and one hospital in El Salvador, between July 2012 and December 2014. Diagnosis of histoplasmosis and cryptococcosis in PLHIV were performed by culture and Ag test., Results: A total of 160 PLHIV were diagnosed with fungal OI, of which, 96 (60%) were diagnosed with histoplasmosis, 62 (39%) were with cryptococcosis, and two patients (1%) were diagnosed with both fungal diseases. Of the 160 patients analysed in this study, 94 (59%) were diagnosed using only an Ag assay. CD4 cell count data were available for 136 (85%) patients; 127 (93%) patients had a CD4 count <200; and 90 (66%) had counts <50 CD4 cells per µl. Antiretroviral therapy utilisation at diagnosis was low (33%). Seventy-one out of 160 (44%) were co-infected with tuberculosis or other OIs., Conclusion: More than half of the patients in this study were diagnosed only by rapid laboratory Ag tests. A high per cent of the patients had advanced HIV disease., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.)

Objectives: To describe the impact of the coronavirus disease 2019 (COVID-19) pandemic on the diagnosis of human immunodeficiency virus (HIV) and deaths from opportunistic infections in Guatemala., Methods: A retrospective study was conducted to investigate the impact of the COVID-19 pandemic on people with HIV at a referral clinic (Clinica Familiar Luis Angel García, CFLAG), as well as the disruption of services at a diagnostic laboratory hub (DLH) which provides diagnosis for opportunistic infections to a network of 13 HIV healthcare facilities. Comparative analysis was undertaken using the months March-August from two different time periods: (i) pre-COVID-19 (2017-2019); and (ii) during the COVID-19 period (2020)., Results: During the COVID-19 period, 7360 HIV tests were performed at Clinica Familiar Luis Angel García, compared with an average of 16,218 tests in the pre-COVID-19 period; a reduction of 54.7% [95% confidence interval (CI) 53.8-55.4%],Deaths from opportunistic infections at 90 days were 10.7% higher in 2020 compared with 2019 (27.3% vs 16.6%; P = 0.05). Clinical samples sent to the DLH for diagnosis of opportunistic infections decreased by 43.7% in 2020 (95% CI 41.0-46.2%)., Conclusion: The COVID-19 pandemic is having a substantial impact on HIV care in Guatemala. Diagnostic services for HIV have been severely affected and deaths from opportunistic infections have increased. The lessons learnt must guide the introduction of strategies to reduce the impact of the pandemic., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Opportunistic infections (OIs) and advanced HIV disease (AHD) contribute to HIV-related mortality. Here, we analyzed the situation of AHD and OIs in a cohort of newly diagnosed HIV patients from Guatemala. We included 2127 adult patients from 13 facilities across the country during 2017 to 2018. Patients were screened for tuberculosis (TB), nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcal disease, independently of their CD4 cell count. Of the 2127 enrolled patients, 1682 (79.1%) had a CD4 cell count available; of which 52% presented with AHD. Of the Mayan population, 65% had AHD. The overall OI incidence was 21%. Histoplasmosis was the most frequent OI (7.9%), followed by TB (7.1%); 94.4% of these infections occurred in patients with a CD4 < 350 cells/mm 3 . Mortality at 180 days was significantly higher in those with OIs than without OIs (29.7% vs. 5.9%, p < 0.0001). In one year, this program decreased the OI mortality by 7% and increased the OI treatment by 5.1%. Early OI diagnosis and appropriate therapy reduced OI mortality among newly diagnosed HIV patients in Guatemala. Screening for OIs should be considered in all newly diagnosed HIV patients who have a CD4 cell count < 350 cells/mm 3 or those without a CD4 cell count available. To improve results, interventions such as early HIV detection and access to flucytosine and liposomal amphotericin B are required.

Objectives: We evaluated the comparative performance of different assays used in a Diagnostic Laboratory Hub that linked 13 HIV healthcare facilities for the diagnosis of tuberculosis (TB), histoplasmosis, and cryptococcosis, and describing its functions in Guatemala compared with other National Reference Laboratories., Methods: The following diagnostic techniques were analyzed in 24 months (2017-2018) in a cohort of patients with HIV: smear microscopy, mycobacterial and fungal cultures, isolator blood culture, PCR assays, and antigen detection tests., Results: A total of 4245 patients were included, 716 (16.2%) had an opportunistic infection: 249 (34.7%) TB, 40 (5.6%) nontuberculous mycobacteria, 227 (31.7%) histoplasmosis, 138 (19.3%) cryptococcosis, and 62 (8.6%) had multiple opportunistic infections. Two hundred sixty-three [92.6%; 95% confidence interval (CI), 89-95.1] of TB cases were diagnosed by PCR. Urine antigen assay detected 94% (95% CI, 89-96) of the disseminated histoplasmosis cases. A lateral flow assay to detect cryptococcal antigen diagnosed 97% (95% CI, 93.3-98.7%) of the cryptococcal cases. In 85 patients (51.5%) with a cerobrospinal fluid sample, cryptococcal meningitis was diagnosed in 55 (64.7%), of which 18 (32.7%) were only detected by cryptococcal antigen., Conclusion: Validated commercial antigen tests, as used in this program, should be the new gold standard for histoplasmosis and cryptococcosis diagnosis. In their absence, 35% of disseminated histoplasmosis and 32.7% of cryptococcal meningitis cases would have been missed. Patients with multiple opportunistic infections were frequently diagnosed and strategies should be designed to screen patients irrespective of their clinical presentation. In low resource settings, Diagnostic Laboratory Hubs can deliver quality diagnostics services in record time at affordable prices.

Disseminated histoplasmosis is a major opportunistic infection of HIV-infected patients, killing thousands in Latin America each year. Yet, it remains a neglected disease that is often confused with tuberculosis, for lack of simple, affordable, and rapid diagnostic tools. There is great heterogeneity in the level of histoplasmosis awareness. The purpose of this report was to describe how the historical "awakening" to the threat of histoplasmosis came to be in four different centers that have actively described this disease: In Brazil, the Sao José hospital in Fortaleza; in Colombia, the Corporación para Investigaciones Biológicas in Medellin; in French Guiana, Cayenne Hospital; and in Guatemala, the Association de Salud Integral in Guatemala city. In Brazil and French Guiana, the search for leishmaniasis on the buffy coat or skin smears, respectively, led to the rapid realization that HIV patients were suffering from disseminated histoplasmosis. With time and progress in fungal culture, the magnitude of this problem turned it into a local priority. In Colombia and Guatemala, the story is different because for these mycology centers, it was no surprise to find histoplasmosis in HIV patients. In addition, collaborations with the CDC to evaluate antigen-detection tests resulted in researchers and clinicians developing the capacity to rapidly screen most patients and to demonstrate the very high burden of disease in these countries. While the lack of awareness is still a major problem, it is instructive to review the ways through which different centers became histoplasmosis-aware. Nevertheless, as new rapid diagnostic tools are becoming available, their implementation throughout Latin America should rapidly raise the level of awareness in order to reduce the burden of histoplasmosis deaths.

Whole-genome sequencing has resulted in new insights into the phylogeography of Mycobacterium tuberculosis However, only limited genomic data are available from M. tuberculosis strains in Guatemala. Here we report 16 complete genomes of clinical strains belonging to the Euro-American lineage 4, the most common lineage found in Guatemala and Central America., (Copyright © 2018 Saelens et al.)

Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients ≥ 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria. A confirmed case of histoplasmosis was defined as a person with a positive culture or urine antigen test for Histoplasma capsulatum . Demographic and clinical data were also collected and analyzed. Of 263 enrolled as suspected cases of histoplasmosis, 101 (38.4%) were confirmed cases. Median time to diagnosis was 15 days after presentation (interquartile range [IQR] = 5-23). Crude overall mortality was 43.6%; median survival time was 19 days (IQR = 4-69). Mycobacterial infection was diagnosed in 70 (26.6%) cases; 26 (25.7%) histoplasmosis cases were coinfected with mycobacteria. High mortality and short survival time after initial symptoms were observed in patients with histoplasmosis. Mycobacterial coinfection diagnoses were frequent, highlighting the importance of pursuing diagnoses for both diseases.

Objective: VIOLIN (TMC125IFD3002; NCT01422330) evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients., Methods: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks) who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL) or simplification/adverse events (viral load < 50 copies/mL) received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors., Results: Of 211 treated patients, 73% (n = 155) had baseline viral load ⩾ 50 copies/mL and 27% (n = 56) had baseline viral load < 50 copies/mL. Protease inhibitors were the most common background antiretrovirals (83%). Diarrhea was the most frequent adverse event (17%). Serious adverse events (no rash) occurred in 5% of patients; none were etravirine related. Overall, median etravirine AUC 12h was 5390 ng h/mL and C 0h was 353 ng/mL (N = 199). Week 48 virologic response rates (viral load < 50 copies/mL; Food and Drug Administration Snapshot algorithm) were 48% (74/155) (baseline viral load ⩾ 50 copies/mL) and 75% (42/56) (baseline viral load < 50 copies/mL). Virologic failure rates were 42% and 13%, respectively. The most frequently emerging etravirine resistance-associated mutations in virologic failures were Y181C, E138A, and M230L. Virologic response rates for patients with baseline viral load ⩾ 50 copies/mL were 38% (30/79) (non-adherent) versus 64% (44/69) (adherent subset)., Conclusion: Etravirine 200 mg bid in combination with antiretrovirals other than darunavir/ritonavir was well tolerated in the studied treatment-experienced HIV-1-infected population. The overall etravirine safety and tolerability profile and pharmacokinetics (specifically in those patients who were adherent) were similar to those previously observed for etravirine in HIV-1-infected adults. The relatively high level of non-adherence, also observed in the pharmacokinetic assessments, negatively impacted virologic response, especially in patients with ⩾50 copies/mL at baseline., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: H.C., L.T., S.V., and M.O. are full-time employees of Janssen. L.L. and B.V.B. are consultants at Janssen. E.A., A.B., and R.S. declare no conflicts of interest or financial disclosures.

Background: Most patients in Guatemala are diagnosed with advanced HIV disease. Patients that present late in the disease process may miss the morbidity and mortality benefits associated with early treatment and may unknowingly spread HIV to others., Research Questions: We examined trends in HIV detection and levels of immunosuppression at diagnosis from 2005 -2012 to determine if expanded HIV testing was associated with earlier detection of HIV., Setting: This study was conducted at the Clínica Familiar Luis Ángel García (CFLAG), a major HIV center associated with one of Guatemala's two national hospitals. HIV testing expanded rapidly after 2007 due to grants from the Global Fund which allowed for routine prenatal testing., Methods: This study examined existing hospital and clinic databases from to evaluate results from HIV tests performed, and baseline CD4 cells/mm(3) on all patients newly diagnosed with HIV infection from 2005 to 2012., Results: We found a decline in the number of HIV positive tests over the study period despite an increase in the total number of tests performed. Sixty-two percent of HIV infected individuals had AIDS at diagnosis. We observed a decrease in median CD4 cells/mm(3) among the prenatal testees and no change in non-prenatal testees., Discussion: Expanded HIV counseling and testing services in our clinic did not result in earlier HIV diagnosis., (© The Author(s) 2016.)

Unlabelled: Coccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region., Importance: Coccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a likely anthropogenic movement of C. posadasii from North America to South America. Here we comparatively analyze eighty-six genomes of the two Coccidioides species and establish local and species-wide population structures to not only clarify the earlier dispersal hypothesis but also provide evidence of likely ancestral populations and patterns of dispersal for the known subpopulations of C. posadasii., (Copyright © 2016 Engelthaler et al.)

Limited data are available regarding the molecular epidemiology of Mycobacterium tuberculosis (Mtb) strains circulating in Guatemala. Beijing-lineage Mtb strains have gained prevalence worldwide and are associated with increased virulence and drug resistance, but there have been only a few cases reported in Central America. Here we report the first whole genome sequencing of Central American Beijing-lineage strains of Mtb. We find that multiple Beijing-lineage strains, derived from independent founding events, are currently circulating in Guatemala, but overall still represent a relatively small proportion of disease burden. Finally, we identify a specific Beijing-lineage outbreak centered on a poor neighborhood in Guatemala City., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction. The MANGUA cohort is an ongoing multicenter, observational study of people living with HIV/AIDS in Guatemala. The cohort is based on the MANGUA application which is an electronic database to capture essential data from the medical records of HIV patients in care. Methods. The cohort enrolls HIV-positive adults ≥16 years of age. A predefined set of sociodemographic, behavioral, clinical, and laboratory data are registered at entry to the cohort study. Results. As of October 1st, 2012, 21 697 patients had been included in the MANGUA cohort (median age: 33 years, 40.3% female). At enrollment 74.1% had signs of advanced HIV infection and only 56.3% had baseline CD4 cell counts. In the first 12 months after starting antiretroviral treatment 26.9% (n = 3938) of the patients were lost to the program. Conclusions. The implementation of a cohort of HIV-positive patients in care in Guatemala is feasible and has provided national HIV indicators to monitor and evaluate the HIV epidemic. The identified percentages of late presenters and high rates of LTFU will help the Ministry to target their current efforts in improving access to diagnosis and care.

Introduction: In DUET, etravirine (ETR) 200 mg bid had durable efficacy and a favourable safety profile versus placebo, both arms with an optimised background regimen (BR) including darunavir/ritonavir (DRV/r). TMC125IFD3002 (VIOLIN; NCT01422330) investigated ETR plus ARVs other than DRV/r., Materials and Methods: This was a 48 week, Phase IV, open-label, single-arm, multicentre study. HIV-1-infected treatment-experienced adult patients on=8 weeks ARV therapy prior to screening, switching either for virologic failure (VF) (viral load [VL] =500 c/mL) or regimen simplification/AEs (RS/AE) (VL<50 c/mL), received active ETR 200 mg bid with an investigator-selected BR of =1 active ARVs, but excluding DRV/r or NRTIs only. The primary objective was to evaluate safety, tolerability and pharmacokinetics (PK)., Results: Of 211 treated patients, 55% were female, 61% black/African American. 155 patients (73%) had baseline (BL) VL=50 c/mL versus 56 (27%) with BL VL<50 c/mL. Between these two latter subgroups, median BL VL was 4.42 versus 1.28 log10 c/mL and CD4+ count 238 versus 410.5 cells/mm(3). Overall, 96% previously used <2 NNRTIs and 99% used=5 PIs; median number of BL NNRTI RAMs was 2, PI RAMs 5 and NRTI RAMs 1. Overall, most common BR ARVs were PIs (83%), mostly lopinavir/r (62%) and mostly used alone (20%) or with 1 or 2 NRTIs (61%). Raltegravir was used in 9% of patients. Most frequent AEs (any cause/grade) were diarrhoea (17%) and URTI (8%). Incidence of grade 3-4 AEs was 13%, serious AEs 5% (no rashes; none ETR related), AEs leading to discontinuation 4%, AEs possibly related to ETR 23% and AEs of interest: rash (any type) 4%, hepatic 6% and neuropsychiatric 3%. At week 48, VF and RS/AE virologic responses (% patients with VL<50 c/mL; FDA Snapshot) were: 48% (74/155) and 75% (42/56), respectively. VF rates were 42% and 13%; 10% and 13% had no VL data in the week 48 window. The percentage of patients adherent to treatment (assessed based on PK sampling plus ETR pill count) was 47% (69/148) and 57% (30/53), in VF and RS/AE, respectively. Median CD4+ count (NC=F) increases were 0.0 and 24.0 cells/mm(3). In 29/49 of VFs with genotypic data at failure, ETR RAMs emerging in =5 patients were Y181C, E138A and M230L. The geometric mean ETR AUC12h was 4877 ng.h/mL and C0h 293 ng/mL (N=199)., Conclusions: RESULTS of this study were consistent with those for ETR in other similar populations and support the use of ETR 200 mg bid with a non-DRV/r based BR.

Highly active antiretroviral therapy regimens, consisting of a ritonavir-boosted protease inhibitor (PI) and 2 nucleoside reverse transcriptase inhibitors, are established first-line regimens for HIV-infected patients. However, a common adverse effect in patients receiving PIs is dyslipidemia, characterized by increases in plasma levels of triglycerides, low-density lipoprotein cholesterol, and total cholesterol (TC). These lipid changes, as well as other well-described risk factors, may predispose patients to the development of cardiovascular disease, an important comorbidity, especially as the lifespan of HIV-infected patients has increased dramatically in recent years. Among PIs, ritonavir-boosted atazanavir (ATV/r) and, more recently, ritonavir-boosted darunavir (DRV/r) have demonstrated potent antiviral efficacy with more favorable lipid profiles than other PIs. This review provides an overview of the lipid effects of DRV/r. Studies with DRV/r in healthy volunteers and in both treatment-naïve and -experienced patients have demonstrated that changes in tri-glycerides and TC are comparable to those seen with ATV/r.

An otherwise healthy 65-year-old male from a rural area presented with a 1-month old non-tender scalp mass. He had a history of being stuck with a stone in the parietal region a year earlier but hadn't developed any complications. Needle aspiration of the mass revealed numerous yeast cells, which were confirmed to be Cryptoccus neoformans. This case describes a rare presentation of C. neoformans infection in a human immunodeficiency virus (HIV)-negative patient. Moreover, while osteomyelitis due to Cryptococcus is generally preceded by fungemia, in the present case it was caused by direct inoculation of the etiologic agent. We review 11 similar cases published since 1983 in which most of the patients developed an insidious mass in their scalps with osteolytic lesions as seen on X-ray and all were HIV-negative. Nine of the eleven patients in these cases had good recovery after surgical debridement and treatment with amphotericin B, flucytocise and/or fluconazole. The remaining two patients died during hospitalization. Cryptococcal osteomyelitis should be part of a differential diagnosis when confronted with an insidious growing mass or abscess of unclear origin in the scalp., (© 2011 ISHAM)

Background: Numerous studies have demonstrated that, in addition to inherent qualities of antiretroviral (ARV) medications, adherence is affected by demographic, socioeconomic, and psychological factors. There are limited data about factors affecting adherence to antiretroviral therapy (ART) among HIV-infected persons in urban Guatemalan HIV care centers., Methods: Participants were patients at an urban, free-care public clinic in Guatemala City and obtained medications from a closed-pharmacy system. Nonpregnant patients ≥18 years who received medications from the Global Fund to Fight AIDS, Tuberculosis & Malaria, who had taken ARV medications for ≥12 weeks, who arrived for an appointment at the clinic, and who provided informed consent were interviewed. Adherence was measured using pharmacy pill counts and patient self-reports. Recent biological markers for each patient were collected from the clinic's database, and χ( 2) and descriptive statistics were used to analyze results., Results: Among 122 patients interviewed, mean adherence by pill count was 97%. A total of 110 patients (90%) had adherence ≥95% using pharmacy pill counts, and 108 (89%) had adherence ≥95% using self-reports. Virologic failure (viral load [VL] ≥500 copies/mL) was significantly less common among patients with ≥95% adherence (P = .02). Family and spousal support for treatment were significantly associated with ≥95% adherence (P = .01 and .003, respectively). The presence of stavudine (d4T) in a patient's regimen was significantly associated with <95% adherence according to self-reports (P < .01). The most common self-reported cause for missing medications was forgetfulness, followed by leaving medications at home. Inability to travel to the clinic was a major cause of missing medications, and only 51 patients (41.8%) reported always having sufficient economic resources to reach the clinic for appointments and to refill prescriptions., Conclusions: In this urban Central American population, high levels of adherence were measured by both self-report and pharmacy pill count. Socioeconomic and demographic conditions associated with adherence and specific reasons for missing medications were identified.

Background: sexually transmitted infection (STI) screening in pregnancy provides an excellent opportunity for secondary prevention., Objective: to document the epidemiology of HIV, hepatitis B, and syphilis among pregnant women at a Guatemalan national hospital., Results: from 2004 to 2009, 118 (0.76%) of 15 563 of women tested in the prenatal clinic had HIV infection, 29 (0.22%) of 13 028 women tested had hepatitis B virus infection, and 78 (0.60%) of 13 027 had a positive test for syphilis. From August 1, 2007 through December 31, 2009, 29 482 women were tested in the obstetrical emergency room. A total of 63 were HIV positive (0.21%), 48 had hepatitis B (0.16%), and 196 had syphilis (0.66%). Of the 9196 births between August 2007 and July of 2008, 33 (0.36%) were to HIV-infected mothers., Conclusion: these 3 STIs were uncommon in our population and did not increase in incidence during the study period. HIV maternal-to-child transmission (MTCT) prevention programs were feasible in our setting.

Objective: We examined the impact of HIV voluntary counseling and testing on self-reported behavioral risks three months after HIV testing., Design: Cohort study comparing self-reported risk behaviors prior to and three months after HIV testing., Setting: Clinica Familiar Luis Angel Garcia, an HIV specialty clinic located in a Guatemalan National Hospital., Subjects, Participants: 144 people undergoing HIV testing were enrolled. 44 were HIV positive. 41 HIV positive and 49 HIV negative subjects returned for follow-up interviews., Intervention: All subjects were tested and received voluntary counseling regarding HIV infection, transmission, prevention, and interpretation of HIV test results., Main Outcome Measure: The primary study outcome measure was change in self-reported risk behaviors three months after voluntary counseling and testing., Results: Men were more likely than women to report a history of sexually transmitted diseases, more than 2 sexual partners, using alcohol with sex, and receiving money for sex; they were less likely to have a regular partner. 26% of men reported non-heterosexual orientation; no woman did. Alcohol was the primary drug of abuse in both men and women. At three month follow-up HIV positive subjects showed decreases in the average number of sexual partners, use of alcohol with sex, and episodes of unprotected sex., Conclusions: Voluntary counseling and testing resulted in changes in some self-reported risk behaviors, but only among HIV positive subjects. On nearly all measures men report riskier behavior than women. Alcohol is the most commonly used drug in this population and is often used with sex.

Histoplasma capsulatum infection causes significant morbidity and mortality in human immunodeficiency virus-infected individuals, particularly those in countries with limited access to rapid diagnostics or antiretroviral therapies. The fungus easily disseminates in persons with AIDS, resulting in progressive disseminated histoplasmosis (PDH), which can progress rapidly to death if undiagnosed. The availability of a simple, rapid method to detect H. capsulatum infection in less developed countries where the infection is endemic would dramatically decrease the time to diagnosis and treatment of PDH. We have developed an antigen-capture enzyme-linked immunosorbent assay (ELISA) to detect PDH antigenuria in infected patients. The assay uses polyclonal antibodies against H. capsulatum as both capture and detection reagents, and a standard reference curve is included to quantify antigenuria and ensure reproducibility. We evaluated this assay using specimens collected from patients with AIDS and culture-proven histoplasmosis in a Guatemalan clinic (n = 48), from healthy persons (n = 83), and from patients with other, nonhistoplasmosis diseases (n = 114). The ELISA demonstrated a sensitivity of 81% and a specificity of 95% in detecting H. capsulatum antigen in urine. This assay relies on simple technology that can be performed in institutions with limited resources. Use of this test will facilitate rapid diagnosis of PDH in countries where mortality is high, expediting treatment and likely reducing PDH-related mortality.

Little is known about the effect of human immunodeficiency virus (HIV) infection on the Central American healthcare system. We describe HIV-related admissions in a Guatemalan medical service. The study was conducted at Guatemala City's largest public hospital. Data were derived from standardized data collection sheets maintained by the HIV testing service and by HIV clinic physicians. Data were collected for 295 medicine admissions of 257 HIV-infected adults during an 18-month period in 1999 and 2000; 30% of the patients were women. Average age was 33 years. Only 12.5% of the patients had been diagnosed with HIV infection prior to 1999 and nearly all had symptomatic AIDS. 60.3% of the patients were diagnosed with HIV infection during their hospitalization. The most common discharge diagnoses were tuberculosis (13.9%), toxoplasmosis, diarrhoea, candida and other fungal infections, and meningitis. Mean length of stay for HIV-positive patients was 17 days. 23.7% of the patients died during their hospitalization; this was double the mortality of non-HIV patients. HIV-infected patients represented 5.8% of the total admissions of the general medical wards. In a country where HIV prevalence is thought to be less than 1%, AIDS is now responsible for over 5% of admissions to a large medical service at a cost of $500,000 per year. These findings underline the importance of HIV infection in Central America and demonstrate the utility of tracking hospital admission data as a method of surveillance.

Caspofungin is a new broad-spectrum antifungal drug. A multicenter, double-blind, randomized trial was conducted to assess the efficacy, safety, and tolerability of caspofungin relative to amphotericin B in adults with endoscopically documented symptomatic Candida esophagitis. By use of a modified intent-to-treat analysis, endoscopically verified clinical success was achieved in 74% (95% confidence interval [CI], 59%-86%) and 89% (95% CI, 72%-98%) of patients receiving caspofungin at 50 and 70 mg/day, respectively, and in 63% (95% CI, 49%-76%) of patients given amphotericin B at 0.5 mg/kg/day. Therapy was stopped because of drug-related adverse events in 24% of patients in the amphotericin B group and 4% and 7%, respectively, for the caspofungin groups. This report provides the first demonstration of clinical utility for an echinocandin compound. Caspofungin appeared in this study to be as effective as and better tolerated than amphotericin B for the treatment of esophageal candidiasis.

Central America is an area with a growing human immunodeficiency virus (HIV) epidemic, but with marked limitations in its health care infrastructure. Estimated adult HIV infection rates range from 0.20% in Nicaragua to 2.01% in Belize. Hospitals and clinicians with experience in HIV care exist mainly, if not only, in capital cities and principal economic centers. Nationally sponsored social security systems in each country consistently offer a wider range of services than do ministry of health systems. Estimated access to the social security system ranges from 0% in Belize and 10% of the population in Honduras to 95% in Costa Rica. Combination antiretroviral therapy is not available through the ministries of health and zidovudine is only sporadically available for prevention of perinatal transmission. Combination therapy is available through the social security system in the countries of Guatemala, Panama, and Costa Rica only. A wide variety of antiretroviral agents are available through private pharmacies in all countries except Belize. With the exception of Costa Ricans, most people with HIV infection in Central America have limited access to HIV-specific health services and limited or no access to antiretroviral agents.

Objectives: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine., Design: Two multicenter, open-label, randomized 24-week studies., Methods: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used., Results: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01)., Conclusion: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.