Prevalence and management of drug-drug interactions with antiretroviral treatment in 2069 people living with HIV in rural Tanzania: a prospective cohort study.

OBJECTIVES: Widespread access to antiretroviral therapy (ART) has substantially increased life expectancy in sub-Saharan African countries. As a result, the rates of comorbidities and use of co-medications among people living with HIV are increasing, necessitating a sound understanding of drug-drug interactions (DDIs). We aimed to assess the prevalence and management of DDIs with ART in a rural Tanzanian setting. METHODS: We included consenting HIV-positive adults initiating ART in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) between January 2013 and December 2016. DDIs were classified using www.hiv-druginteractions.org as red (contra-indicated), amber (potential clinical relevance requiring dosage adjustment/monitoring), yellow (weak clinical significance unlikely to require further management) or green (no interaction). We assessed management of amber DDIs by evaluating monitoring of laboratory or clinical parameters, or changes in drug dosages. RESULTS: Of 2069 participants, 1945 (94%) were prescribed at least one co-medication during a median follow-up of 1.8 years. Of these, 645 (33%) had at least one potentially clinically relevant DDI, with the highest grade being red in nine (< 1%) and amber in 636 (33%) participants. Of the 23 283 prescriptions, 19 (< 1%) and 1745 (7%) were classified as red and amber DDIs, respectively. Overall, 351 (2%) prescriptions were red DDIs or not appropriately managed amber DDIs. CONCLUSIONS: Co-medication use was common in this rural sub-Saharan cohort. A third of participants had DDIs requiring further management. Of the 9% of participants with not appropriately managed DDIs, most were with cardiovascular and analgesic drugs. This highlights the importance of physicians' awareness of DDIs for their recognition and management.

Prevalence rates of six selected infectious diseases among African migrants and refugees: a systematic review and meta-analysis.

The objective of this paper was to systematically review the literature on the prevalence of selected infectious diseases among migrants/refugees of African origin and to provide policy makers and health care professionals with evidence-based information. We pursued a systematic review and meta-analysis to determine the prevalence of six selected infectious diseases (i.e., syphilis, helminthiasis, schistosomiasis, intestinal protozoa infections, hepatitis B, and hepatitis C) among migrants/refugees of African origin. Three electronic databases (i.e., PubMed, EMBASE, and ISI Web of Science) were searched without language restrictions. Relevant data were extracted and random-effects meta-analyses conducted. Only adjusted estimates were analyzed to help account for heterogeneity and potential confounding. We assessed the quality of evidence using the GRADE approach. The results were stratified by geographical region. Ninety-six studies were included. The evidence was of low quality due to the small numbers of countries, infectious diseases, and participants included. African migrants/refugees had median (with 95% confidence interval [95% CI]) prevalence for syphilis, helminthiasis, schistosomiasis, intestinal protozoa infection, hepatitis B, and hepatitis C of 6.0% [95% CI: 2.0-7.0%], 13.0% [95% CI: 9.5-14.5%], 14.0% [95% CI: 13.0-17.0%], 15.0% [95% CI: 10.5-21.0%], 10.0% [95% CI: 6.0-14.0%], and 3.0% [95% CI: 1.0-4.0%], respectively. We found high heterogeneity regardless of the disease (I 2; minimum 97.5%, maximum 99.7%). The relatively high prevalence of some infectious diseases among African migrants/refugees warrants for systematic screening. The large heterogeneity of the available published data does not allow for stratifying such screening programs according to the geographical origin of African migrants/refugees.

Coagulation and inflammation in scrub typhus and murine typhus--a prospective comparative study from Laos.

Scrub typhus (caused by Orientia tsutsugamushi) and murine typhus (caused by Rickettsia typhi) cause up to 28% of febrile episodes in Thailand and Laos. The current understanding of coagulation and inflammation in the pathogenesis of these clinically very similar vasculotropic diseases is limited. This study compared human in vivo changes in 15 coagulation, inflammation and endothelial activation markers in prospectively collected admission and follow-up samples of 121 patients (55 scrub typhus, 55 murine typhus, and 11 typhus-like illness) and 51 healthy controls from Laos. As compared with controls, all but one of the markers assessed were significantly affected in typhus patients; however, the activation patterns differed significantly between scrub and murine typhus patients. The levels of markers of coagulation activation and all inflammatory cytokines, except for interleukin-12, were significantly higher in patients with scrub typhus than in those with murine typhus. In patients with murine typhus, however, the levels of endothelium-derived markers were significantly higher. Anticoagulant factors were inhibited in both typhus patient groups. This is the first study demonstrating that, in scrub typhus, in vivo coagulation activation is prominent and is related to a strong proinflammatory response, whereas in murine typhus, changes in coagulant and fibrinolytic pathways are suggestive of endothelial cell perturbation. These data suggest that, although late-stage endothelial infection is common in both diseases, the in vivo pathogenic mechanisms of R. typhi and O. tsutsugamushi could differ in the early phase of infection and may contribute to disease differentiation.

A highly sensitive quantitative real-time PCR assay based on the groEL gene of contemporary Thai strains of Orientia tsutsugamushi.

Partial nucleotide sequences (459 bp) of the groEL gene (encoding the 60-kDa heat shock protein, HSP60) from 23 contemporary isolates of Orientia tsutsugamushi isolated from patients with acute scrub typhus in Thailand were compared with 16 reference strain sequences to evaluate the potential of groEL as a conserved and representative target for molecular diagnostics.. Overall nucleotide identity within all available O. tsutsugamushi isolates (n = 39) was 98.8% (range: 95.0-100), reflecting a high degree of conservation; nucleotide identities were 67.5% and 65.6%, respectively, when typhus and spotted fever group rickettsiae were included.. A highly sensitive and quantitative real-time PCR assay was designed and evaluated using 61 samples, including buffy coats from patients in Thailand and Laos. Reliable and accurate quantitation of bacterial loads allows further investigation of other diagnostic methods and may lead to an improved understanding of the pathophysiology of acute scrub typhus, an important but under-recognized disease.

Differential patterns of endothelial and leucocyte activation in 'typhus-like' illnesses in Laos and Thailand.

Scrub typhus is responsible for a large proportion of undifferentiated fevers in south-east Asia. The cellular tropism and pathophysiology of the causative agent, Orientia tsutsugamushi, remain poorly understood. We measured endothelial and leucocyte activation by soluble cell adhesion molecule enzyme-linked immunosorbent assays in 242 Lao and Thai patients with scrub or murine typhus, leptospirosis, dengue, typhoid and uncomplicated falciparum malaria on admission to hospital. Soluble E-selectin (sE-selectin) levels were lowest in dengue, sL-selectin highest in scrub typhus with a high sE-selectin to sL-selectin ratio in leptospirosis patients. In scrub typhus patients elevated sL-selectin levels correlated with the duration of skin rash (P = 0.03) and the presence of eschar (P = 0.03), elevated white blood cell (WBC) count (P = 0.007), elevated lymphocyte (P = 0.007) and neutrophil counts (P = 0.015) and elevated levels of sE-selectin correlated with the duration of illness before admission (P = 0.03), the presence of lymphadenopathy (P = 0.033) and eschar (P = 0.03), elevated WBC (P = 0.005) and neutrophil counts (P = 0.0003). In comparison, soluble selectin levels in murine typhus patients correlated only with elevated WBC counts (P = 0.03 for sE-selectin and sL-selectin). Soluble intercellular adhesion molecule-1 and soluble vascular adhesion molecule-1 levels were not associated significantly with any clinical parameters in scrub or murine typhus patients. The data presented suggest mononuclear cell activation in scrub typhus. As adhesion molecules direct leucocyte migration and induce inflammatory and immune responses, this may represent O. tsutsugamushi tropism during early dissemination, or local immune activation within the eschar.