High Endemic Settings Research Articles

Awareness and low uptake of post exposure prophylaxis for HIV among clinical medical students in a high endemicity setting.

BackgroundAdequate knowledge and practices on post exposure prophylaxis (PEP) for HIV among health care providers are crucial for HIV prevention. However there is limited data on PEP knowledge and practice from developing countries where the burden of HIV infection continues to increase. We assessed the knowledge of clinical medical students on PEP, their practices in response to occupational exposure to HIV, as well as the determinants of good knowledge on PEP.MethodsA cross-sectional study was conducted in November 2014 involving 154 consecutively recruited clinical medical students (4th-6th year undergraduates). Data were acquired using a structured questionnaire. Knowledge on PEP was assessed using a questionnaire comprising 25 questions and categorized as: good (20 or more correct answers), moderate (13–19 correct answers) and poor (12 or fewer correct answers).ResultsFor the 154 students included (57.8 % being male), the mean age was 23.2 ± 2.4 years, and 89 % had heard about PEP for HIV. The majority of students had moderate (61.7 %) and poor (32.5 %) knowledge on PEP. Overall knowledge score increased with increasing level of studies (p < 0.05). Only 10 (6.5 %) had had previous training on PEP, most of whom were senior level students (p = 0.01). Fifty-four students (35.1 %) knew the appropriate duration of PEP and this awareness increased with level of studies (p = 0.001). Of the 81 (52.6 %) who reported occupational exposure to HIV in the past, only 4 (4.9 %) received PEP.ConclusionsOverall, knowledge on PEP among clinical medical students in this setting was non-optimal with very low uptake PEP. Intensification of HIV curricula to involve PEP as well as continuous medical education programs and workshops are potential avenues to improve awareness in this vulnerable population.

Evaluation of Giant African Pouched Rats for Detection of Pulmonary Tuberculosis in Patients from a High-Endemic Setting.

BackgroundThis study established evidence about the diagnostic performance of trained giant African pouched rats for detecting Mycobacterium tuberculosis in sputum of well-characterised patients with presumptive tuberculosis (TB) in a high-burden setting.MethodsThe TB detection rats were evaluated using sputum samples of patients with presumptive TB enrolled in two prospective cohort studies in Bagamoyo, Tanzania. The patients were characterised by sputum smear microscopy and culture, including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis, and by clinical data at enrolment and for at least 5-months of follow-up to determine the reference standard. Seven trained giant African pouched rats were used for the detection of TB in the sputum samples after shipment to the APOPO project in Morogoro, Tanzania.ResultsOf 469 eligible patients, 109 (23.2%) were culture-positive for Mycobacterium tuberculosis and 128 (27.3%) were non-TB controls with sustained recovery after 5 months without anti-TB treatment. The HIV prevalence was 46%. The area under the receiver operating characteristic curve of the seven rats for the detection of culture-positive pulmonary tuberculosis was 0.72 (95% CI 0.66–0.78). An optimal threshold could be defined at ≥2 indications by rats in either sample with a corresponding sensitivity of 56.9% (95% CI 47.0–66.3), specificity of 80.5% (95% CI 72.5–86.9), positive and negative predictive value of 71.3% (95% CI 60.6–80.5) and 68.7% (95% CI 60.6–76.0), and an accuracy for TB diagnosis of 69.6%. The diagnostic performance was negatively influenced by low burden of bacilli, and independent of the HIV status.ConclusionGiant African pouched rats have potential for detection of tuberculosis in sputum samples. However, the diagnostic performance characteristics of TB detection rats do not currently meet the requirements for high-priority, rapid sputum-based TB diagnostics as defined by the World Health Organization.

Spatial Patterns of Plasmodium falciparum Clinical Incidence, Asymptomatic Parasite Carriage and Anopheles Density in Two Villages in Mali.

Heterogeneity in malaria exposure is most readily recognized in areas with low-transmission patterns. By comparison, little research has been done on spatial patterns in malaria exposure in high-endemic settings. We determined the spatial clustering of clinical malaria incidence, asymptomatic parasite carriage, and Anopheles density in two villages in Mali exposed to low- and mesoendemic-malaria transmission. In the two study areas that were < 1 km(2) in size, we observed evidence for spatial clustering of Anopheles densities or malaria parasite carriage during the dry season. Anopheles density and malaria prevalence appeared associated in some of our detected hotspots. However, many households with high parasite prevalence or high Anopheles densities were located outside the identified hotspots. Our findings indicate that within small villages exposed to low- or mesoendemic-malaria transmission, spatial patterns in mosquito densities and parasite carriage are best detected in the dry season. Considering the high prevalence of parasite carriage outside detected hotspots, the suitability of the area for targeting control efforts to households or areas of more intense malaria transmission may be limited.

Global Epidemiology of Hepatitis B Virus (HBV) Infection

Infection with hepatitis B virus (HBV) remains a top health priority worldwide and a devastating cause of morbidity and mortality accounting for more than 600,000 deaths in 2013. It is mainly transmitted through percutaneous or mucosal contact with infected blood or other body fluids. In high-endemic settings, the commonest route of transmission is from infected mothers to neonates, whereas in areas of low endemicity the infection is mostly acquired during adolescence and early adulthood through high-risk behaviors. More than 350 million are chronically infected with HBV, ranging from 80 % coverage globally has resulted in a steady decline in the prevalence of HBV. However, there are remaining threats to the successful eradication of HBV worldwide. We review available data on global epidemiology of HBV infection, also focusing on transmission modes by region and specific preventative measures instituted.

PCR for enteric pathogens in high-prevalence settings. What does a positive signal tell us?

Background: Molecular methods, in particular PCR, are increasingly used for the diagnosis of enteric pathogens in stool samples. In high-endemicity settings, however, asymptomatic carriage or residual DNA from previous infections will hamper the interpretation of positive test results. We assessed the quantitative dimension of this problem in schoolchildren in the rural highlands of Madagascar. Methods: Stool samples were collected from 410 apparently healthy Madagascan schoolchildren and analysed by multiplex real-time PCR for enteroinvasive bacteria (Salmonella spp., Shigella spp./enteroinvasive Escherichia coli (EIEC), Campylobacter jejuni, Yersinia spp.), enteric protozoa (Entamoebea histolytica, Giardia duodenalis, Cryptosporidium spp., Cyclospora spp.), and helminths (Ascaris lumbricoides, Ancylostoma spp., Necator americanus, Strongyloides stercoralis). Symptoms of gastrointestinal disease were assessed. Results: Among the 410 samples, we detected Giardia duodenalis in 195, Campylobacter jejuni in 91, Ascaris lumbricoides in 72, Cyclospora cayetanenesis in 68, Shigella spp./EIEC in 56, and Strongyloides stercoralis and Cryptosporum spp. in 1 case each. Salmonella spp., Yersinia spp. and hookworms were not observed. Relative risk assessment suggested few and incoherent associations with pathogen detections, indicating asymptomatic carriage or DNA residuals. Only 26.1% of the schoolchildren were tested negative for all analysed pathogens. Conclusions: The very high risk of detecting traces of asymptomatic carriage or residual DNA from previous infections limits the value of highly sensitive PCR for the causal attribution of detected enteric pathogens from stool samples to an infectious gastrointestinal disease in the high-endemicity setting. Evaluated standards for the interpretation of such results are needed both for the diagnostic routine and for epidemiological assessments.

Determinants of Immunization Among Children Aged 12-23 Months in Ethiopia: A Proportional Odds Model Approach

Childhood immunization is recognized as one of the most cost-effective public health interventions to prevent morbidity and mortality caused by infectious diseases, particularly in a high-endemic setting. According to the 2011 EDHS report by the Central Statistical Agency (CSA) of Ethiopia, nationally, only 24 percent of children age 12-23 months was fully immunized at the time of the survey. The main objective of this study was to identify and describe the determinants of immunization among children aged 12-23 months in Ethiopia. The source of the data was the Ethiopian Demographic and Health Survey conducted in 2011 (EDHS) 2011. In order to meet our objectives descriptive, and ordinal logistic regression (proportional odds model) statistical techniques were used for data analysis using socio-economic and demographic variables as explanatory variables and immunization status of children aged 12-23 months as the response variable. The results of the analysis predicts that place of delivery, wealth index, possession of radio and region were found to be significant determinants for full immunization among children aged 12-23 months in Ethiopia.

Characteristics of rural leptospirosis patients admitted to referral hospitals during the 2008 leptospirosis outbreak in Sri Lanka: implications for developing public health control measures.

To determine the exposure risk factors of highly endemic rural leptospirosis in tropical setting, we conducted a prospective, hospital-based case control study in Sri Lanka. A conceptual hierarchy of variables was used to analyze the data. Case patients included 38 (34%) females and 73 (66%) males with a mean age of 36 yr (SD 12.7 yr). Using piped, chlorinated water for drinking/general purposes (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.16-0.67), paddy fields in the vicinity of home (OR 1.77, 95% CI 1.06-2.97), sighting dogs at home yard/dog ownership (OR 1.79, 95% CI 1.11-2.91), sighting cattle at home yard/cattle ownership (OR 1.69, 95% CI 1.00-2.84), and work in a paddy field (OR 3.02, 95% CI 1.68, 5.41) were the main predictors of leptospirosis among febrile patients. In high endemic tropical settings with rural leptospirosis, risk factors in residential environments, rather than individual exposures, seemed to play a major role in leptospirosis disease transmission.

A 24-well plate assay for simultaneous testing of first and second line drugs against Mycobacterium tuberculosis in a high endemic setting

BackgroundEarly detection of drug resistance is one of the priorities of tuberculosis (TB) control programs as drug resistance is increasing. New molecular assays are only accessible for a minority of the second line drugs and their availability in high endemic settings is also hampered by high cost and logistic challenges. Therefore, we evaluated a previously developed method for drug susceptibility testing (DST) including both first- and second line anti-TB drugs for use in high endemic areas.ResultsBaseline mycobacterial isolates from 78 consecutive pulmonary TB patients from Addis Ababa, Ethiopia who were culture positive for Mycobacterium tuberculosis at the end of a two-month directly observed treatment short course (DOTS) were included. The isolates were simultaneously tested for isoniazid, rifampicin, ethambutol, streptomycin, amikacin, kanamycin, capreomycin, ofloxacin, moxifloxacin, ethionamide and para-aminosalicylic acid susceptibility using the indirect proportion method adopted for 24-well agar plates containing Middlebrook 7H10 medium. Applying the 24-well plate assay, 43 (55.1%) isolates were resistant to one or more of the first line drugs tested (isoniazid, rifampicin and ethambutol). MDR-TB was identified in 20.5% of this selected group and there was a perfect correlation for rifampicin resistance with the results from the genotype MTBDRplus assay. All isolates were susceptible to aminoglycosides and fluoroquinolones in agreement with the genotype MTBDRsl assay. The only tested second line drug associated to resistance was ethionamide (14.1% resistant). The method was reproducible with stable results for internal controls (one multi-drug resistant (MDR) and one pan-susceptible strain (H37Rv) and DST results could be reported at two weeks.ConclusionsThe 24-well plate method for simultaneous DST for first- and second line drugs was found to be reproducible and correlated well to molecular drug susceptibility tests. It is likely to be useful in high-endemic areas for surveillance as well as for the detection of second line drug resistance in targeted groups such as in those who fail empirical MDR treatment.

The effectiveness of BCG vaccination in preventing Mycobacterium tuberculosis infection and disease in Greenland

BackgroundThe BCG vaccine's ability to prevent Mycobacterium tuberculosis infection (MTI) remains highly debated. In Greenland, BCG vaccination was introduced in 1955, but was temporarily discontinued (1991–1996) due to nationwide policy...

Cryptococcal meningitis: epidemiology and therapeutic options.

Cryptococcal meningitis causes morbidity and mortality worldwide. The burden of disease is greatest in middle- and low-income countries with a high incidence of human immunodeficiency virus (HIV) infection. Patients taking immunosuppressive drugs and some immunocompetent hosts are also at risk. Treatment of cryptococcal meningitis consists of three phases: induction, consolidation, and maintenance. Effective induction therapy requires potent fungicidal drugs (amphotericin B and flucytosine), which are often unavailable in low-resource, high-endemicity settings. As a consequence, mortality is unacceptably high. Wider access to effective treatment is urgently required to improve outcomes. For human immunodeficiency virus-infected patients, judicious management of asymptomatic cryptococcal antigenemia and appropriately timed introduction of antiretroviral therapy are important.

Re-Assessing Tuberculin Skin Test (TST) for the Diagnosis of Tuberculosis (TB) among African Migrants in Western Europe and USA

Background: Tuberculin skin test (TST)—is widely used for screening tuberculosis TB in migrants from high endemic countries of Africa and Asia. However, the cut-off point for clinical TB and Mtb infection is not well established in TB endemic countries of sub-Saharan Africa. In this study we compared the size of TST induration in smear positive pulmonary TB (PTB) patients, their house-hold contacts and community controls in high endemic setting in Ethiopia. Methods: In a health facility-based cross-sectional study, smear positive PTB patients were recruited. Their household contacts traced, and community controls were recruited from neighbourhoods. Sputum sample collected from patients were examined using smear microscopy. Participants were also tested by TST and QuantiFERON? -TB Gold In–Tube test (QFTGIT). Results: From a total of 224 study participants, skin test induration data were available for 48 PTB patients, 88 household contacts and 75 community controls. All 48 patients, 64 (72.2%) of the household contacts and 35 (46.7%) of the community controls had skin test induration ≥ 10 mm. Moreover, 44 (91.7%) PTB patients, 58 (65.9%) of the household contacts and 26 (34.7%) of the community controls had skin test induration ≥ 15 mm, respectively. The mean size of TST induration was significantly higher in TB patients (18.1mm) compared to that of household contacts (13.6 mm) and community controls (7.9 mm) (pMtb infection

Cost–benefit of infection control interventions targeting methicillin-resistant Staphylococcus aureus in hospitals: systematic review

AbstractInfections caused by methicillin-resistant Staphylococcus aureus (MRSA) incur significant costs. We aimed to examine the cost and cost-benefit of infection control interventions against MRSA and to examine factors affecting economic estimates. We performed a systematic review of studies assessing infection control interventions aimed at preventing spread of MRSA in hospitals and reporting intervention costs, savings, cost-benefit or cost-effectiveness. We searched PubMed and references of included studies with no language restrictions up to January 2012. We used the Quality of Health Economic Studies tool to assess study quality. We report cost and savings per month in 2011 US$. We calculated the median save/cost ratio and the save-cost difference with interquartile range (IQR) range. We examined the effects of MRSA endemicity, intervention duration and hospital size on results. Thirty-six studies published between 1987 and 2011 fulfilled inclusion criteria. Fifteen of the 18 studies reporting both costs and savings reported a save/cost ratio >1. The median save/cost ratio across all 18 studies was 7.16 (IQR 1.37–16). The median cost across all studies reporting intervention costs (n = 31) was 8648 (IQR 2025–19 170) US$ per month; median savings were 38 751 (IQR 14 206–75 842) US$ per month (23 studies). Higher save/cost ratios were observed in the intermediate to high endemicity setting compared with the low endemicity setting, in hospitals with <500-beds and with interventions of >6 months. Infection control intervention to reduce spread of MRSA in acute-care hospitals showed a favourable cost/benefit ratio. This was true also for high MRSA endemicity settings. Unresolved economic issues include rapid screening using molecular techniques and universal versus targeted screening.

Loop Mediated Isothermal Amplification (LAMP) for Rapid Diagnosis of Tuberculous Lymphatics: In High Endemic Low Recourse Settings

Loop Mediated Isothermal Amplification (LAMP) for Rapid Diagnosis of Tuberculous Lymphatics: In High Endemic Low Recourse Settings

O077: The impact of a multi-faceted approach on the reduction of peripheral line-associated MRSA bloodstream infections in a high endemic setting

The Mediterranean region is characterized by a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI). Following root cause analysis (RCA) of MRSA BSI cases, Mater Dei Hospital, a tertiary care institution in Malta, identified that a 30% of healthcare associated (HA) MRSA BSI from April 2010 to December 2011 were associated with Peripheral Venous Catheters (PVC).

Progressive ocular inflammation following anti-tubercular therapy for presumed ocular tuberculosis in a high-endemic setting

To analyze the incidence and clinical course of patients developing progressive ocular inflammation following anti-tubercular therapy (ATT) for presumed ocular tuberculosis (TB). Retrospective analysis of medical records of patients who received ATT for presumed ocular TB and completed at least 12 months follow-up after initiation of ATT. The diagnosis of presumed ocular TB was based on presence of ocular signs suggestive of TB, evidence of past tubercular infection, and exclusion of mimicking clinical entities. All patients received a combination of ATT and corticosteroid therapy. Primary outcome measure was progression (worsening) of ocular inflammation, defined as a two-step increase in level of inflammation (anterior chamber/ vitreous) or the appearance of new lesions following initiation of ATT. A total of 106 patients (64 male, 42 female) received ATT for presumed ocular TB. Twenty-six (24.5%) patients developed progressive intraocular inflammation following ATT. Primary diagnoses in these patients were: anterior uveitis (n=1), intermediate uveitis (n=9), retinal vasculitis (n=3), serpiginous-like choroiditis (n=7), multifocal choroiditis (n=2), and pan-uveitis (n=4). Following progressive inflammation, diagnosis was revised in two patients (7.7%)-both responded to alternative therapy. Of the rest, majority (n=16; 61.5%) resolved with escalation of corticosteroid therapy. Five patients (19.2%)-all having intermediate uveitis-required therapeutic vitrectomy for resolution. Three patients (11.5%) had persistent inflammation at end of follow-up period. Progressive inflammation following ATT for presumed ocular TB is common. It generally resolves on escalation of corticosteroid therapy. Cases not responding to increased immunosuppression need to be re-investigated to rule out a nontubercular cause.

Multiplex analysis of cytokines/chemokines as biomarkers that differentiate healthy contacts from tuberculosis patients in high endemic settings

Differentiation of latent tuberculosis infection (LTBI) from active disease is one of the crucial elements in the control of tuberculosis. Earlier in Indian population which is tuberculosis endemic, we identified that 10 Mycobacterium tuberculosis secreted protein fractions, induced IFN-γ response only in healthy contacts of TB patients (HCs) and not in tuberculosis patients (TB). These fractions were termed as “Contact Specific Fractions” (“CS” fractions) and found useful for differentiating HC from TB. Proteomic analysis revealed that “CS” fractions have 16 different proteins, of which three were novel T cell antigens. Using these “CS” fractions as stimulants, earlier IFN-γ, TNF-α and IL-4 cytokine responses were studied. In the present study, in order to identify the other useful cytokine biomarkers that were differentially expressed between HC and TB, Cytokine/chemokine response to “CS” fractions were analyzed using multiplex cytokine assay system. This preliminary investigation in our tuberculosis endemic population showed six cytokine (G-CSF, IL-6, IL-7, IL-8, IL-9, and PDGF) and one receptor antagonist (IL-1Ra) that were differentially expressed between HC and TB, for the first time. Especially IL-6 and PDGF were more promising biomarkers. IL-6 measurement identified seven as HC out of 10 HC analyzed. The measurement of PDGF identified eight as TB out of 10TB tested. Studies are underway to further validate these biomarkers for the differentiation of LTBI from active tuberculosis.

Comparative durability of nevirapine versus efavirenz in first-line regimens during the first year of initiating antiretroviral therapy among Swaziland HIV-infected adults

Nevirapine (NVP) and Efavirenz (EFV) have generally comparable clinical and virologic efficacy. However, data comparing NVP durability to EFV are imprecise. We analyzed cohort data to compare durability of NVP to EFV among patients initiating ART in Mbabane, Swaziland. The primary outcome was poor regimen durability defined as any modification of NVP or EFV to the ART regimen. Multivariate Cox proportional hazards models were employed to estimate the risk of poor regimen durability (all-cause) for the two regimens and also separately to estimate risk of drug-related toxicity. We analyzed records for 769 patients initiating ART in Mbabane, Swaziland from March 2006 to December 2007. 30 patients (3.9%) changed their NVP or EFV-based regimen during follow up. Cumulative incidence for poor regimen durability was 5.3% and 2.7% for NVP and EFV, respectively. Cumulative incidence for drug-related toxicity was 1.9% and 2.7% for NVP and EFV, respectively. Burden of TB was high and 14 (46.7%) modifications were due to patients substituting NVP due to beginning TB treatment. Though the estimates were imprecise, use of NVP - based regimens seemed to be associated with higher risk of modifications compared to use of EFV - based regimens (HR 2.03 95%CI 0.58 - 7.05) and NVP - based regimens had a small advantage over EFV - based regimens with regard to toxicity - related modifications (HR 0.87 95%CI 0.26 - 2.90). Due to the high burden of TB and a significant proportion of patients changing their ART regimen after starting TB treatment, use of EFV as the preferred NNRTI over NVP in high TB endemic settings may result in improved first-line regimen tolerance. Further studies comparing the cost-effectiveness of delivering these two NNRTIs in light of their different limitations are required.

Decolonization of patients and health care workers to control nosocomial spread of methicillin-resistant Staphylococcus aureus:a simulation study

BackgroundControl of methicillin-resistant Staphylococcus aureus (MRSA) transmission has been unsuccessful in many hospitals. Recommended control measures include isolation of colonized patients, rather than decolonization of carriage among patients and/or health care workers. Yet, the potential effects of such measures are poorly understood.MethodsWe use a stochastic simulation model in which health care workers can transmit MRSA through short-lived hand contamination, or through persistent colonization. Hand hygiene interrupts the first mode, decolonization strategies the latter. We quantified the effectiveness of decolonization of patients and health care workers, relative to patient isolation in settings where MRSA carriage is endemic (rather than sporadic outbreaks in non-endemic settings caused by health care workers).ResultsPatient decolonization is the most effective intervention and outperforms patient isolation, even with low decolonization efficacy and when decolonization is not achieved immediately. The potential role of persistently colonized health care workers in MRSA transmission depends on the proportion of persistently colonized health care workers and the likelihood per colonized health care worker to transmit. As stand-alone intervention, universal screening and decolonization of persistently colonized health care workers is generally the least effective intervention, especially in high endemicity settings. When added to patient isolation, such a strategy would have maximum benefits if few health care workers cause a large proportion of the acquisitions.ConclusionsIn high-endemicity settings regular screening of health care workers followed by decolonization of MRSA-carriers is unlikely to reduce nosocomial spread of MRSA unless there are few persistently colonized health care workers who are responsible for a large fraction of the MRSA acquisitions by patients. In contrast, decolonization of patients can be very effective.

The Effect of Age on Whole Blood Interferon-Gamma Release Assay Response among Children Investigated for Latent Tuberculosis Infection

To evaluate the effect of age upon QuantiFERON-TB Gold-In-Tube (QFT-IT) assay outcome among children examined for latent tuberculosis infection (LTBI). A cross-sectional study was conducted among 761 children (mean age ± SD: 7.84 ± 4.68 years) evaluated for LTBI. Participants were examined with both tuberculin skin test and QFT-IT (Cellestis, Australia) and categorized into 4 age groups. Multivariate logistic and linear regressions were used to evaluate the association between selected demographic and patient characteristics upon the qualitative and quantitative QFT-IT outcomes. Agreement between the tuberculin skin test and QFT-IT within groups was evaluated with the κ statistic. QFT-IT indeterminate results occurred more frequently among young children (8.1%; P < .0001) and children (2.7%; P = .025) than adolescents (0.7%). Among QFT-IT positive patients, infants had higher mean (± SD) interferon-gamma (IFNγ) concentration than adolescents. QFT-IT positive (vs negative) outcome was associated with origin from a high tuberculosis endemicity setting (AOR = 4.54; 95% CI, 3.22-6.25) and lack of previous Bacille Calmette Guerin immunization (AOR = 2.70; 95% CI, 1.89-3.85), but not patient age (AOR = 0.96; 95% CI, 0.92-0.99). However, among QFT-IT positive patients, the IFNγ concentration was inversely associated with patient age (P = .009) and positively with mitogen response (P = .0002). Agreement between tests was not significantly different between younger and older children in the different risk groups. Qualitative QFT-IT assay results are not affected by patient age. However, indeterminate results occur more frequently among younger children. Among patients with LTBI the quantitative QFT-IT result (ie, IFNγ) is inversely associated with patient age.

Beate Kampmann: research advocate for children with tuberculosis

Beate Kampmann: research advocate for children with tuberculosis