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The causes of antimicrobial resistance (AMR) in developing countries are complex and may be rooted in practices of health care professionals and patients’ behavior towards the use of antimicrobials as well as supply chains of antimicrobials in the population. Some of these factors may include inappropriate prescription practices, inadequate patient education, limited diagnostic facilities, unauthorized sale of antimicrobials, lack of appropriate functioning drug regulatory mechanisms, and non-human use of antimicrobials such as in animal production. Considering that these factors in developing countries may vary from those in developed countries, intervention efforts in developing countries need to address the context and focus on the root causes specific to this part of the world. Here, we describe these health-seeking behaviors that lead to the threat of AMR and healthcare practices that drive the development of AMR in developing countries and we discuss alternatives for disease prevention as well as other treatment options worth exploring.

Background We investigated the effects of mutations K65R and K65R plus M184V on enzymatic function and mechanisms of drug resistance in subtype C reverse transcriptase (RT). Methods Recombinant subtype C HIV-1 RTs containing K65R or K65R+M184V were purified from Escherichia coli . Enzyme activities and tenofovir (TFV) incorporation efficiency by wild-type (WT) and mutant RTs of both subtypes were determined in cell-free assays. Efficiency of (-) ssDNA synthesis and initiation by subtype C RTs was measured using gel-based assays with HIV-1 PBS RNA template and tRNA3 Lys as primer. Single-cycle processivity was assayed under variable dNTP concentrations. Steady-state analysis was performed to measure the relative inhibitory capacity (ki/km) of TFV-disphosphate (TFV-DP). ATP-dependent excision and rescue of TFV-or ZDV-terminated DNA synthesis was monitored in time-course experiments. Results The efficiency of tRNA-primed (-)ssDNA synthesis by subtype C RTs was: WT > K65R > K65R+M184V RT. At low dNTP concentration, K65R RT exhibited lower activity in single-cycle processivity assays while the K65R+M184V mutant showed diminished processivity independent of dNTP concentration. ATP-mediated excision of TFV-or ZDV-terminated primer was decreased for K65R and for K65R+M184V RT compared to WT RT. K65R and K65R+M184V displayed 9.8-and 5-fold increases in IC50 for TFV-DP compared to WT RT. The Ki/Km of TFV was increased by 4.1-and 7.2-fold, respectively, for K65R and K65R+M184V compared to WT RT. Conclusion The diminished initiation efficiency of K65R-containing RTs at low dNTP concentrations have been confirmed for subtype C as well as subtype B. Despite decreased excision, this decreased binding/incorporation results in diminished susceptibility of K65R and K65R+M184 RT to TFV-DP.

Background: Rotaviruses are the primary cause of acute gastroenteritis in young children worldwide and a significant proportion of these infections occur in Africa.Objectives: In the present study, we determined the prevalence and risk factors of rotavirus infection among children younger than age 5 years with or without diarrhoea in Calabar, Nigeria, using a rapid point-of-care test.Methods: Two hundred infants younger than age 5 years presenting with acute gastroenteritis and a control group of 200 infants without diarrhoea were tested for rotavirus. Each stool sample was homogenised in an extraction buffer and the supernatant added into the sample well of the Rida Quick rotavirus test cassette and allowed to run for 5 minutes at room temperature. When both the control band and test band were visible on the test cassette a positive result was recorded, whereas when only the control band was visible a negative results was recorded.Results: Rotavirus was detected in 25 (12.5%) of children with diarrhoea and in no children without diarrhoea. Our results demonstrated that children who were exclusively breast-fed by their mothers were not infected with rotavirus and that 92% of the infants infected with rotavirus experienced vomiting.Conclusion: These data demonstrate that asymptomatic rotavirus infection is rare and that rotavirus is commonly detected in stool samples of children suffering from diarrhoea with concomitant vomiting. Use of point-of-care rotavirus tests will enhance early diagnosis of rotavirus-associated diarrhoea and reduce irrational use of antibiotics.

Background. A population-based phylogenetic approach was used to characterize human immunodeficiency virus (HIV)—transmission dynamics in Quebec. Methods. HIV-1 pol sequences included primary HIV infections (PHIs; <6 months after seroconversion) from the Quebec PHI cohort (1998–2005; n = 215) and the provincial genotyping program (2001–2005; n = 481). Phylogenetic analysis determined sequence interrelationships among unique PHIs (n = 593) and infections from untreated (n = 135) and treated (n = 660) chronically infected (CI) potential transmitter populations (2001–2005). Clinical features, risk factors, and drug resistance for clustered and nonclustered transmission events were ascertained. Results. Viruses from 49.4% (293/593) of PHIs cosegregated into 75 transmission chains with 2–17 transmissions/cluster. Half of the clusters included 2.7 ± 0.8 (mean ± SD) transmissions, whereas the remainder had 8.8 ± 3.5 transmissions. Maximum periods for onward transmission in clusters were 15.2 ± 9.5 months. Coclustering of untreated and treated CIs with PHIs were infrequent (6.2% and 4.8%, respectively). The ages, viremia, and risk factors were similar for clustered and nonclustered transmission events. Low prevalence of drug resistance in PHI supported amplified transmissions at early stages. Conclusions. Early infection accounts for approximately half of onward transmissions in this urban North American study. Therapy at early stages of disease may prevent onward HIV transmission.

Objective a) To assess the suitability of the curriculum content and didactical quality of information delivered to educate journalists in the J2J program in HIV/AIDS (process evaluation) and b) to explore the effects of such programs on journalists' reporting of HIV/AIDS related information (outcome evaluation). Design Descriptive study. Methods For the process evaluation, each J2J program curriculum was evaluated for accuracy and pertinence by individuals with high familiarity with HIV/AIDS research. For the outcome evaluation, a survey of J2J attendees and evaluations of the program lectures by attendees were performed in chronological order to determine their perception on usefulness of the program. Results Overall, the J2J curriculum is successful in providing journalists with a clear understanding of the current HIV/AIDS medical research objectives and issues with most journalists reporting an increased ability to better investigate and disseminate accurate information on this subject. Furthermore, the journalists surveyed reported positive community responses directly as a result of the J2J training. Conclusion The J2J program helps to increase global awareness of pertinent HIV/AIDS concepts. Through this professional development strategy, journalists from around the world may help to amplify efforts to prevent new HIV infections and quench the dissemination of inaccurate information and folklore.

This doctoral thesis includes four projects. The first project explored the role of innate HIV genetic polymorphisms in drug-selected mutations. By means of drug selection experiments, we comparatively evaluated emergent mutations in protease and reverse transcriptase in HIV-1 and HIV-2 subtypes. Genotypic and phenotypic analyses were used to determine time to appearance of resistance mutations and the levels of drug resistance, respectively. Natural polymorphisms in HIV-2 seemed to facilitate selection of protease inhibitor (PI) resistance: The acquisition of the I54M, I84V, L90M and L99F mutations resulted in multi-PI-resistant viruses. Nucleoside reverse transcriptase inhibitor (NRTI) combinations preferentially selected for the K65R mutation in HIV-1 subtype C, while in HIV-1 subtype B, and HIV-2 cultures favored the development of M1841. The K65R mutation was not detected in HIV-2 selections. These results underscore potential differences in emergent drug resistance pathways in HIV-1 and HIV-2 and the role that innate polymorphisms may have in dictating antiretroviral resistance pathways. In the second project, we studied the relationship between mutations in the RNase H domain on viral susceptibility to nucleoside analogues. Our results showed that although some mutations were observed in the connection domain, the presence of the L74V and M184V mutations was the most significant determinant of phenotypic resistance to ZDV in patients with thymidine analog-associated mutations. The third project performed a near full-length genomic analysis of a novel HIV-1 recombinant involving subtypes A1 and C in Quebec. The fourth project evaluated the genetic diversity of an HIV-1 isolate that was referred to us as a suspected case of superinfection. We evaluated this isolate's sequences from different time points and determined that the sequence was a unique A1/C intersubtype recombinant at baseline and not a case of superinfection. We concluded that discrepancies of online tools for subtype designation of HIV may lead to false designation of dual infection and/or superinfection.