In order to characterize A/H5N1 viral sequences, a bioinformatics approach accurately identified ... more In order to characterize A/H5N1 viral sequences, a bioinformatics approach accurately identified viral sequences from discovery of a sequence signature, which provided enough distinctive information for sequence identification. Eight highly pathogenic H5N1 viral isolations were collected from different areas of Thailand between 2003 and 2006, and were used for analysis of H5N1 genotypic testing with a semiconductor-based oligonucleotide microarray. All H5N1 samples and H1N1, H4N8 negative controls were correctly subtyped. Sensitivity of the eight oligonucleotide probes, with optimized cut-offs, ranged from 70% (95% CI 65-75) to 87% (95% CI 84-91), and the corresponding Kappa values ranged from 0.76 (95% CI 0.72-0.80) to 0.86 (95% CI 0.83-0.89). Semi-conductor-based oligonucleotide array and oligonucleotide probes corresponded well when detecting H5N1. After fully correcting the subtype from the result of microarray signal intensity, the microarray output method combined with bioinformatics tools, identified and monitored genetic variations of H5N1. Capability of distinguishing different strains of H5N1 from Thailand was the outstanding feature of this assay. Ninety percent of HA and NA (4/5) genes were sequenced correctly, in accordance with previous examinations performed by classical diagnostic methods. The low-medium-high bioinformatics resolutions were able to predict an epidemic strain of H5N1. This study also showed the advantage of using a large genotypic database to predict the epidemic strain of H5N1. However, the monitoring protocol of this new strain has been recommended for further study with a large-scale sample.
Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguis... more Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. Eight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5's had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence. Hb began to fall after treatment start. In under 5's the estimated nadir was ~35 h (range 29-48), with a drop o...
This study investigates trends and age-and-sex patterns of mortality in pulmonary tuberculosis (P... more This study investigates trends and age-and-sex patterns of mortality in pulmonary tuberculosis (PTB) and PTB/HIV co-infection in a rural population of South Africa. The PTB/HIV mortality emerged in 1994, and has been rising ever since (men: P = 0.001; women: P = 0.020, test for trend). In the last 2 years, for both sexes combined, 63% (95% CI 51—74%) of PTB deaths were attributable to HIV/AIDS. PTB/HIV death rate was higher in men than in women for all ages combined (RR MH = 2.48, 95% CI 1.53—4.04, P < 0.001). PTB/HIV death rate was also higher in younger individuals (<25 years) compared with PTB without HIV/AIDS (P = 0.033), and the median age at death from PTB/HIV in women (28 years) was lower than in men (38 years, P = 0.002). While mortality from PTB without HIV remained constant over time, HIV/AIDS explained the rise in PTB mortality. In the last 3 years, the HIV/AIDS epidemic has caused the number of persons dying of PTB to increase by +117%, with the mortality excess being higher in women (+164%) than in men (+103%, P = 0.001). Combined PTB and HIV programme activities need to be reinforced to respond to the increase in PTB mortality, particularly in women.
African Journal of Reproductive Health, Aug 1, 2008
The paper investigates the complex relationships between premarital fertility and HIV/AIDS in sub... more The paper investigates the complex relationships between premarital fertility and HIV/AIDS in sub-Saharan African countries. The DHS surveys provided data to compute the prevalence of premarital fertility, defined as any birth before the first marriage. The UNAIDS database provided data to compute the prevalence of HIV infection among pregnant women. Results indicate a moderate association between the prevalence of premarital fertility and the prevalence of HIV infection (correlation coefficient = 0.64, P < 0.0001), and similar geographical patterns. Compared with the average pattern, outlier countries had either high levels of premarital fertility and relatively low HIV prevalence (Liberia, Madagascar, Gabon, Congo), or high levels of HIV prevalence despite low levels of premarital fertility (Lesotho, Malawi, Zambia, Zimbabwe). The overall relationship is discussed in light of the relationships between age at marriage, permissiveness and lack of protection during intercourse and their impact on premarital fertility and HIV infection among women.
A qualitative study was conducted in Agincourt, a rural area of South Africa, to document the per... more A qualitative study was conducted in Agincourt, a rural area of South Africa, to document the perceptions and attitudes towards premarital fertility and late marriage among young adults of both sexes. Two focus groups and 35 individual interviews were conducted among 17-30 year olds, randomly selected. Most interviewees perceived premarital fertility as undesirable, and a new phenomenon in a context of major social changes, in particular loss of authority of parents and increasing freedom of the youth. In contrast, late marriage was perceived as positive, by both sexes, primarily for economic reasons. Much stigma was associated with premarital fertility, from friends, institutions and families who occasionally apply mild or severe sanctions. Consequences of premarital fertility were numerous: school abandonment, economic adversity, health risks, stigmatization. In extreme cases, premarital fertility might lead to exclusion and deviant behavior. Premarital fertility was ultimately du...
The paper investigates the complex relationships between premarital fertility and HIV/AIDS in sub... more The paper investigates the complex relationships between premarital fertility and HIV/AIDS in sub-Saharan African countries. The DHS surveys provided data to compute the prevalence of premarital fertility, defined as any birth before the first marriage. The UNAIDS database provided data to compute the prevalence of HIV infection among pregnant women. Results indicate a moderate association between the prevalence of premarital fertility and the prevalence of HIV infection (correlation coefficient = 0.64, P < 0.0001), and similar geographical patterns. Compared with the average pattern, outlier countries had either high levels of premarital fertility and relatively low HIV prevalence (Liberia, Madagascar, Gabon, Congo), or high levels of HIV prevalence despite low levels of premarital fertility (Lesotho, Malawi, Zambia, Zimbabwe). The overall relationship is discussed in light of the relationships between age at marriage, permissiveness and lack of protection during intercourse and...
One main etiology for oral squamous cell carcinoma (OSCC) is inflammation. Inducible nitric oxide... more One main etiology for oral squamous cell carcinoma (OSCC) is inflammation. Inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) are the important molecules showing close relation to not only inflammation but also carcinogenesis and angiogenesis. Angiogenesis is defined as the formation of new blood vessels from existing vasculature. It is necessary for tumor growth and
Premarital fertility, defined as birth before first marriage, is investigated in Madagascar, usin... more Premarital fertility, defined as birth before first marriage, is investigated in Madagascar, using two Demographic and Health Surveys (DHS) conducted in 1992 and 1997. About 8 per cent of all births and 23 per cent of first births take place before marriage, despite a low underlying mean age at first marriage, estimated to be 18.6 years in the absence of
Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensi... more Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different Schistosoma species. A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any Schistosoma species assessed within two months post-treatment. Of 273 studies identified, 55 were eligible (19,499 subjects treated with praziquantel, control treatment or placebo). Most studied were in school-aged children (64%), S. mansoni (58%), and the 40 mg/kg dose (56%); 68% of subjects were in Africa. Efficacy was assessed as cure rate (CR, n=17,017) and egg reduction rate (ERR, n=13,007); safety as adverse events (AE) incidence. The WHO-recommended dose of praziquantel 40 mg/kg achieved CRs of 94.7% (95%CI 92.2-98.0) for S. japonicum, 77.1% (68.4-85.1) for S. haematobium, 76.7% (95%CI 71.9-81.2) for S. mansoni, and 63.5% (95%CI 48.2-77.0) for mixed S. haematobium/S. mansoni i...
The American journal of tropical medicine and hygiene, 2006
Artemether-lumefantrine is the first registered, fixed, artemisinin-based combination treatment. ... more Artemether-lumefantrine is the first registered, fixed, artemisinin-based combination treatment. Artemisinin derivatives are highly effective antimalarials with a favorable safety profile. Concerns remain over their potential neurotoxicity, although there has been no clinical evidence of this in humans. In animals (rats, dogs, and monkeys) artemether, a derivative of artemisinin is associated with an unusual toxicity pattern in specific brain nuclei involving the auditory and vestibular pathways. A recent report from Mozambique described a small but significant and irreversible hearing loss in patients exposed to artemether-lumefantrine. To explore this issue, we conducted a case-control study using tympanometry, audiometry and auditory brain-stem responses. We assessed 68 subjects who had been treated with artemether-lumefantrine within the previous five years and 68 age- and sex-matched controls living in the malarious region along the Thailand-Myanmar border. There were no differ...
The fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP) is a promising new... more The fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP) is a promising new artemisinin-based combination therapy (ACT). We present an individual patient data analysis of efficacy and tolerability in acute uncomplicated falciparum malaria, from seven published randomized clinical trials conducted in Africa and South East Asia using a predefined in-vivo protocol. Comparator drugs were mefloquine-artesunate (MAS3) in Thailand, Myanmar, Laos and Cambodia; artemether-lumefantrine in Uganda; and amodiaquine+sulfadoxine-pyrimethamine and artesunate+amodiaquine in Rwanda. In total 3,547 patients were enrolled: 1,814 patients (32% children under five years) received DP and 1,733 received a comparator antimalarial at 12 different sites and were followed for 28-63 days. There was no significant heterogeneity between trials. DP was well tolerated with 1.7% early vomiting. There were less adverse events with DP in children and adults compared to MAS3 except for diarrhea; O...
In order to characterize A/H5N1 viral sequences, a bioinformatics approach accurately identified ... more In order to characterize A/H5N1 viral sequences, a bioinformatics approach accurately identified viral sequences from discovery of a sequence signature, which provided enough distinctive information for sequence identification. Eight highly pathogenic H5N1 viral isolations were collected from different areas of Thailand between 2003 and 2006, and were used for analysis of H5N1 genotypic testing with a semiconductor-based oligonucleotide microarray. All H5N1 samples and H1N1, H4N8 negative controls were correctly subtyped. Sensitivity of the eight oligonucleotide probes, with optimized cut-offs, ranged from 70% (95% CI 65-75) to 87% (95% CI 84-91), and the corresponding Kappa values ranged from 0.76 (95% CI 0.72-0.80) to 0.86 (95% CI 0.83-0.89). Semi-conductor-based oligonucleotide array and oligonucleotide probes corresponded well when detecting H5N1. After fully correcting the subtype from the result of microarray signal intensity, the microarray output method combined with bioinformatics tools, identified and monitored genetic variations of H5N1. Capability of distinguishing different strains of H5N1 from Thailand was the outstanding feature of this assay. Ninety percent of HA and NA (4/5) genes were sequenced correctly, in accordance with previous examinations performed by classical diagnostic methods. The low-medium-high bioinformatics resolutions were able to predict an epidemic strain of H5N1. This study also showed the advantage of using a large genotypic database to predict the epidemic strain of H5N1. However, the monitoring protocol of this new strain has been recommended for further study with a large-scale sample.
Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguis... more Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. Eight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5's had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence. Hb began to fall after treatment start. In under 5's the estimated nadir was ~35 h (range 29-48), with a drop o...
This study investigates trends and age-and-sex patterns of mortality in pulmonary tuberculosis (P... more This study investigates trends and age-and-sex patterns of mortality in pulmonary tuberculosis (PTB) and PTB/HIV co-infection in a rural population of South Africa. The PTB/HIV mortality emerged in 1994, and has been rising ever since (men: P = 0.001; women: P = 0.020, test for trend). In the last 2 years, for both sexes combined, 63% (95% CI 51—74%) of PTB deaths were attributable to HIV/AIDS. PTB/HIV death rate was higher in men than in women for all ages combined (RR MH = 2.48, 95% CI 1.53—4.04, P < 0.001). PTB/HIV death rate was also higher in younger individuals (<25 years) compared with PTB without HIV/AIDS (P = 0.033), and the median age at death from PTB/HIV in women (28 years) was lower than in men (38 years, P = 0.002). While mortality from PTB without HIV remained constant over time, HIV/AIDS explained the rise in PTB mortality. In the last 3 years, the HIV/AIDS epidemic has caused the number of persons dying of PTB to increase by +117%, with the mortality excess being higher in women (+164%) than in men (+103%, P = 0.001). Combined PTB and HIV programme activities need to be reinforced to respond to the increase in PTB mortality, particularly in women.
African Journal of Reproductive Health, Aug 1, 2008
The paper investigates the complex relationships between premarital fertility and HIV/AIDS in sub... more The paper investigates the complex relationships between premarital fertility and HIV/AIDS in sub-Saharan African countries. The DHS surveys provided data to compute the prevalence of premarital fertility, defined as any birth before the first marriage. The UNAIDS database provided data to compute the prevalence of HIV infection among pregnant women. Results indicate a moderate association between the prevalence of premarital fertility and the prevalence of HIV infection (correlation coefficient = 0.64, P < 0.0001), and similar geographical patterns. Compared with the average pattern, outlier countries had either high levels of premarital fertility and relatively low HIV prevalence (Liberia, Madagascar, Gabon, Congo), or high levels of HIV prevalence despite low levels of premarital fertility (Lesotho, Malawi, Zambia, Zimbabwe). The overall relationship is discussed in light of the relationships between age at marriage, permissiveness and lack of protection during intercourse and their impact on premarital fertility and HIV infection among women.
A qualitative study was conducted in Agincourt, a rural area of South Africa, to document the per... more A qualitative study was conducted in Agincourt, a rural area of South Africa, to document the perceptions and attitudes towards premarital fertility and late marriage among young adults of both sexes. Two focus groups and 35 individual interviews were conducted among 17-30 year olds, randomly selected. Most interviewees perceived premarital fertility as undesirable, and a new phenomenon in a context of major social changes, in particular loss of authority of parents and increasing freedom of the youth. In contrast, late marriage was perceived as positive, by both sexes, primarily for economic reasons. Much stigma was associated with premarital fertility, from friends, institutions and families who occasionally apply mild or severe sanctions. Consequences of premarital fertility were numerous: school abandonment, economic adversity, health risks, stigmatization. In extreme cases, premarital fertility might lead to exclusion and deviant behavior. Premarital fertility was ultimately du...
The paper investigates the complex relationships between premarital fertility and HIV/AIDS in sub... more The paper investigates the complex relationships between premarital fertility and HIV/AIDS in sub-Saharan African countries. The DHS surveys provided data to compute the prevalence of premarital fertility, defined as any birth before the first marriage. The UNAIDS database provided data to compute the prevalence of HIV infection among pregnant women. Results indicate a moderate association between the prevalence of premarital fertility and the prevalence of HIV infection (correlation coefficient = 0.64, P < 0.0001), and similar geographical patterns. Compared with the average pattern, outlier countries had either high levels of premarital fertility and relatively low HIV prevalence (Liberia, Madagascar, Gabon, Congo), or high levels of HIV prevalence despite low levels of premarital fertility (Lesotho, Malawi, Zambia, Zimbabwe). The overall relationship is discussed in light of the relationships between age at marriage, permissiveness and lack of protection during intercourse and...
One main etiology for oral squamous cell carcinoma (OSCC) is inflammation. Inducible nitric oxide... more One main etiology for oral squamous cell carcinoma (OSCC) is inflammation. Inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) are the important molecules showing close relation to not only inflammation but also carcinogenesis and angiogenesis. Angiogenesis is defined as the formation of new blood vessels from existing vasculature. It is necessary for tumor growth and
Premarital fertility, defined as birth before first marriage, is investigated in Madagascar, usin... more Premarital fertility, defined as birth before first marriage, is investigated in Madagascar, using two Demographic and Health Surveys (DHS) conducted in 1992 and 1997. About 8 per cent of all births and 23 per cent of first births take place before marriage, despite a low underlying mean age at first marriage, estimated to be 18.6 years in the absence of
Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensi... more Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different Schistosoma species. A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any Schistosoma species assessed within two months post-treatment. Of 273 studies identified, 55 were eligible (19,499 subjects treated with praziquantel, control treatment or placebo). Most studied were in school-aged children (64%), S. mansoni (58%), and the 40 mg/kg dose (56%); 68% of subjects were in Africa. Efficacy was assessed as cure rate (CR, n=17,017) and egg reduction rate (ERR, n=13,007); safety as adverse events (AE) incidence. The WHO-recommended dose of praziquantel 40 mg/kg achieved CRs of 94.7% (95%CI 92.2-98.0) for S. japonicum, 77.1% (68.4-85.1) for S. haematobium, 76.7% (95%CI 71.9-81.2) for S. mansoni, and 63.5% (95%CI 48.2-77.0) for mixed S. haematobium/S. mansoni i...
The American journal of tropical medicine and hygiene, 2006
Artemether-lumefantrine is the first registered, fixed, artemisinin-based combination treatment. ... more Artemether-lumefantrine is the first registered, fixed, artemisinin-based combination treatment. Artemisinin derivatives are highly effective antimalarials with a favorable safety profile. Concerns remain over their potential neurotoxicity, although there has been no clinical evidence of this in humans. In animals (rats, dogs, and monkeys) artemether, a derivative of artemisinin is associated with an unusual toxicity pattern in specific brain nuclei involving the auditory and vestibular pathways. A recent report from Mozambique described a small but significant and irreversible hearing loss in patients exposed to artemether-lumefantrine. To explore this issue, we conducted a case-control study using tympanometry, audiometry and auditory brain-stem responses. We assessed 68 subjects who had been treated with artemether-lumefantrine within the previous five years and 68 age- and sex-matched controls living in the malarious region along the Thailand-Myanmar border. There were no differ...
The fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP) is a promising new... more The fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP) is a promising new artemisinin-based combination therapy (ACT). We present an individual patient data analysis of efficacy and tolerability in acute uncomplicated falciparum malaria, from seven published randomized clinical trials conducted in Africa and South East Asia using a predefined in-vivo protocol. Comparator drugs were mefloquine-artesunate (MAS3) in Thailand, Myanmar, Laos and Cambodia; artemether-lumefantrine in Uganda; and amodiaquine+sulfadoxine-pyrimethamine and artesunate+amodiaquine in Rwanda. In total 3,547 patients were enrolled: 1,814 patients (32% children under five years) received DP and 1,733 received a comparator antimalarial at 12 different sites and were followed for 28-63 days. There was no significant heterogeneity between trials. DP was well tolerated with 1.7% early vomiting. There were less adverse events with DP in children and adults compared to MAS3 except for diarrhea; O...
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Papers by Julien Zwang