Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries

BACKGROUND: Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS: 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naive adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS: Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

Beta-D-glucoside utilization by Mycoplasma mycoides subsp. mycoides SC: possible involvement in the control of cytotoxicity towards bovine lung cells

BACKGROUND: Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subsp. mycoides small-colony type (SC) is among the most serious threats for livestock producers in Africa. Glycerol metabolism-associated H2O2 production seems to play a crucial role in virulence of this mycoplasma. A wide number of attenuated strains of M. mycoides subsp. mycoides SC are currently used in Africa as live vaccines. Glycerol metabolism is not affected in these vaccine strains and therefore it does not seem to be the determinant of their attenuation. A non-synonymous single nucleotide polymorphism (SNP) in the bgl gene coding for the 6-phospho-beta-glucosidase (Bgl) has been described recently. The SNP differentiates virulent African strains isolated from outbreaks with severe CBPP, which express the Bgl isoform Val204, from strains to be considered less virulent isolated from CBPP outbreaks with low mortality and vaccine strains, which express the Bgl isoform Ala204. RESULTS: Strains of M. mycoides subsp. mycoides SC considered virulent and possessing the Bgl isoform Val204, but not strains with the Bgl isoform Ala204, do trigger elevated levels of damage to embryonic bovine lung (EBL) cells upon incubation with the disaccharides (i.e., beta-D-glucosides) sucrose and lactose. However, strains expressing the Bgl isoform Val204 show a lower hydrolysing activity on the chromogenic substrate p-nitrophenyl-beta-D-glucopyranoside (pNPbG) when compared to strains that possess the Bgl isoform Ala204. Defective activity of Bgl in M. mycoides subsp. mycoides SC does not lead to H2O2 production. Rather, the viability during addition of beta-D-glucosides in medium-free buffers is higher for strains harbouring the Bgl isoform Val204 than for those with the isoform Ala204. CONCLUSION: Our results indicate that the studied SNP in the bgl gene is one possible cause of the difference in bacterial virulence among strains of M. mycoides subsp. mycoides SC. Bgl does not act as a direct virulence factor, but strains possessing the Bgl isoform Val204 with low hydrolysing activity are more prone to survive in environments that contain high levels of beta-D-glucosides, thus contributing in some extent to mycoplasmaemia.

Discordant responses to potent antiretroviral treatment in previously naive HIV-1-infected adults initiating treatment in resource-constrained countries: the antiretroviral therapy in low-income countries (ART-LINC) collaboration

OBJECTIVES: To assess the frequency of and risk factors for discordant responses at 6 months on highly active antiretroviral therapy (HAART) in previously treatment-naive HIV patients from resource-limited countries. METHODS: The Antiretroviral Therapy in Low-Income Countries Collaboration is a network of clinics providing care and treatment to HIV-infected patients in Africa, Latin America, and Asia. Patients who initiated therapy between 1996 and 2004, were aged 16 years or older, and had a baseline CD4 cell count were included in this analysis. Responses were defined based on plasma viral load (PVL) and CD4 cell count at 6 months as complete virologic and immunologic (VR(+)IR(+)), virologic only (VR(+)IR(-)), immunologic only (VR(-)IR(+)), and nonresponse (VR(-)IR(-)). Multinomial logistic regression was used to assess the association between therapy responses and clinical and demographic variables. RESULTS: Of the 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VR(+)IR(+), 364 (19.0%) were VR(+)IR(-), 283 (14.8%) were (VR(-)IR(+)), and 193 (10.1%) were VR(-)IR(-). OF THE 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VRIR, 364 (19.0%) were VRIR, 283 (14.8%) were (VRIR), and 193 (10.1%) were VRIR. Compared with complete responders, virologic-only responders were older, had a higher baseline CD4 cell count, had a lower baseline PVL, and were more likely to have received a nonstandard HAART regimen; immunologic-only responders were younger, had a lower baseline CD4 cell count, had a higher baseline PVL, and were more likely to have received a protease inhibitor-based regimen. CONCLUSIONS: The frequency of and risk factors for discordant responses were comparable to those observed in developed countries. Longer follow-up is needed to assess the long-term impact of discordant responses on mortality in these resource-limited settings.

Taxonomic position and geographical distribution of the common sheep G1 and camel G6 strains of Echinococcus granulosus in three African countries

The taxonomic and phylogenetic status of Echinococcus granulosus strains are still controversial and under discussion. In the present study, we investigated the genetic polymorphism of E. granulosus isolates originating from three countries of Africa, including a region of Algeria, where the common G1 sheep and the camel G6 strains coexist sympatrically. Seventy-one hydatid cysts were collected from sheep, cattle, camels, and humans. Two mitochondrial markers (cox1 and nad1) were used for strain identification. Two nuclear markers (actII and hbx2) were used to study the possible occurrence of cross-fertilization. Despite the heterogeneity observed among the G1 isolates, they were all localized within one robust cluster. A second strong cluster was also observed containing all of the G6 isolates. Both strains appeared as two distinct groups, and no cases of interbreeding were found. Thus, the attribution of a species rank can be suggested. We also found the Tasmanian sheep G2 strain for the first time in Africa. Because of the slight variations observed between the common sheep and the Tasmanian sheep strains, further studies should be carried out to elucidate the epidemiological relevance of this genetic discrimination.

Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries

OBJECTIVE: To analyse the early loss of patients to antiretroviral therapy (ART) programmes in resource-limited settings. METHODS: Using data on 5491 adult patients starting ART (median age 35 years, 46% female) in 15 treatment programmes in Africa, Asia and South America with (3) 12 months of follow-up, we investigated risk factors for no follow-up after treatment initiation, and loss to follow-up or death in the first 6 months. FINDINGS: Overall, 211 patients (3.8%) had no follow-up, 880 (16.0%) were lost to follow-up and 141 (2.6%) were known to have died in the first 6 months. The probability of no follow-up was higher in 2003-2004 than in 2000 or earlier (odds ratio, OR: 5.06; 95% confidence interval, CI: 1.28-20.0), as was loss to follow-up (hazard ratio, HR: 7.62; 95% CI: 4.55-12.8) but not recorded death (HR: 1.02; 95% CI: 0.44-2.36). Compared with a baseline CD4-cell count (3) 50 cells/microl, a count < 25 cells/microl was associated with a higher probability of no follow-up (OR: 2.49; 95% CI: 1.43-4.33), loss to follow-up (HR: 1.48; 95% CI: 1.23-1.77) and death (HR: 3.34; 95% CI: 2.10-5.30). Compared to free treatment, fee-for-service programmes were associated with a higher probability of no follow-up (OR: 3.71; 95% CI: 0.97-16.05) and higher mortality (HR: 4.64; 95% CI: 1.11-19.41). CONCLUSION: Early patient losses were increasingly common when programmes were scaled up and were associated with a fee for service and advanced immunodeficiency at baseline. Measures to maximize ART programme retention are required in resource-poor countries.

Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration

AIMS: To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. METHODS: The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. RESULTS: Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. CONCLUSIONS: Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring

BACKGROUND: In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia. DESIGN AND METHODS: Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models. RESULTS: A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1-26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79). CONCLUSION: In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.

Imported malaria in children in industrialized countries, 1992-2002

Children account for an appreciable proportion of total imported malaria cases, yet few studies have quantified these cases, identified trends, or suggested evidence-based prevention strategies for this group of travelers. We therefore sought to identify numbers of cases and deaths, Plasmodium species, place of malaria acquisition, preventive measures used, and national origin of malaria in children. We analyzed retrospective data from Australia, Denmark, France, Germany, Italy, Japan, the Netherlands, Sweden, Switzerland, the United Kingdom, and the United States and data provided by the United Nations World Tourism Organization. During 1992-2002, >17,000 cases of imported malaria in children were reported in 11 countries where malaria is not endemic; most (>70%) had been acquired in Africa. Returning to country of origin to visit friends and relatives was a risk factor. Malaria prevention for children should be a responsibility of healthcare providers and should be subsidized for low-income travelers to high-risk areas.

Mapping H5N1 highly pathogenic avian influenza risk in Southeast Asia

The highly pathogenic avian influenza (HPAI) H5N1 virus that emerged in southern China in the mid-1990s has in recent years evolved into the first HPAI panzootic. In many countries where the virus was detected, the virus was successfully controlled, whereas other countries face periodic reoccurrence despite significant control efforts. A central question is to understand the factors favoring the continuing reoccurrence of the virus. The abundance of domestic ducks, in particular free-grazing ducks feeding in intensive rice cropping areas, has been identified as one such risk factor based on separate studies carried out in Thailand and Vietnam. In addition, recent extensive progress was made in the spatial prediction of rice cropping intensity obtained through satellite imagery processing. This article analyses the statistical association between the recorded HPAI H5N1 virus presence and a set of five key environmental variables comprising elevation, human population, chicken numbers, duck numbers, and rice cropping intensity for three synchronous epidemic waves in Thailand and Vietnam. A consistent pattern emerges suggesting risk to be associated with duck abundance, human population, and rice cropping intensity in contrast to a relatively low association with chicken numbers. A statistical risk model based on the second epidemic wave data in Thailand is found to maintain its predictive power when extrapolated to Vietnam, which supports its application to other countries with similar agro-ecological conditions such as Laos or Cambodia. The model’s potential application to mapping HPAI H5N1 disease risk in Indonesia is discussed.

Bringing high-throughput techniques to orphan crop of Africa: Highlights from the Tef TILLING Project

Orphan- or understudied-crops are mostly staple food crops in developing world. They are broadly classified under cereals, legumes, root crops, fruits and vegetables. These under-researched crops contribute to the diet of a large portion of resource-poor consumers and at the same time generate income for small-holder farmers in developing countries, particularly in Africa. In addition, they perform better than major crops of the world under extreme soil and climatic conditions. However, orphan crops are not without problems. Due to lack of scientific investigation, most of them produce low yields while others have a variety of toxins that affect the health of consumers. Here, we present some highlights on the status and future perspectives of the Tef Biotechnology Project that employs modern improvement technique in order to genetically improve tef (Eragrostis tef), one of the most important orphan crop in Africa. A reverse genetics approach known as TILLING (Targeting Induced Local Lesions IN Genome) is implemented in order to tackle lodging, the major yield limiting factor in tef.Key words: Orphan crops, underresearched crops, Eragrostis tef, TILLING, semi-dwarf.

KIWAKKUKI - Women fight against HIV/AIDS. An encouraging example for social work in Tanzania

For 20 years, AIDS has continued its relentless spread across the globe. By the end of the year 2000, the United Nations’ Joint Programme on HIV/AIDS reported that 36.1 million men, women, and children around the world were living with HIV and 21.8 million had died of it. Though AIDS is now found in every country, it has most seriously affected sub-Saharan Africa - home to 70 % of all adults and 80 % of all children living with HIV, and the continent with the least medical resources in the world. Today, AIDS is the primary cause of death in Africa and it has had a devastating impact on villages, communities and families. In many African countries, the number of newly infected persons is increasing at a rate that is threatening to destroy the social fabric. Life expectancy is decreasing rapidly in many of these countries as a result of AIDS related illnesses and socioeconomic problems. Of the approximately 13.2 million children orphaned by HIV/AIDS worldwide, 12.1 million live in Africa.

Differences in primary sites of infection between zoonotic and human tuberculosis: results from a worldwide systematic review.

Tuberculosis (TB) is one of the most devastating infectious diseases worldwide. Whilst global burden estimates for M. tuberculosis infection (MtTB) are well established, accurate data on the contribution of zoonotic TB (zTB) caused by M. bovis or M. caprae to human TB are scarce. The association of M. bovis infection with extrapulmonary tuberculosis has been suggested repeatedly, though there is little scientific evidence available to support this relationship. The present study aimed to determine globally the occurrence of extrapulmonary TB and the primary site (i.e. primary body location affected) of zTB in comparison with MtTB, based on previously published reports. A systematic literature review was conducted in 32 different bibliographic databases, selecting reports on zTB written in English, French, German, Spanish or Portuguese. Data from 27 reports from Africa, America, Europe and the Western Pacific Region were extracted for analyses. Low income countries, in Africa and South-East Asia, were highly underrepresented in the dataset. The median proportion of extrapulmonary TB cases was significantly increased among zTB in comparison with data from registries of Europe and USA, reporting mainly MtTB cases (47% versus 22% in Europe, 73% versus 30% in the USA). These findings were confirmed by analyses of eight studies reporting on the proportions of extrapulmonary TB in comparable populations of zTB and MtTB cases (median 63% versus 22%). Also, disparities of primary sites of extrapulmonary TB between zTB and MtTB were detected. Our findings, based on global data, confirm the widely suggested association between zTB and extrapulmonary disease. Different disability weights for zTB and MtTB should be considered and we recommend separate burden estimates for the two diseases.

Impact of Baseline Renal Function on Tenofovir-containing Antiretroviral Therapy Outcomes in Zambia

Background. Although tenofovir (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non-TDF-containing ART in Lusaka, Zambia. Methods. We included patients aged ≥16 years who started ART from 2007 onward, with documented baseline weight and serum creatinine. Renal dysfunction was categorized as mild (eGFR 60-89 mL/min), moderate (30-59 mL/min) or severe (<30 mL/min) using the CKD-EPI formula. Differences in eGFR during ART were analyzed using linear mixed-effect models, the odds of developing moderate or severe eGFR decrease with logistic regression and mortality with competing risk regression. Results. We included 62,230 adults, of which 38,716 (62%) initiated a TDF-based regimen. The proportion with moderate or severe renal dysfunction at baseline was lower in the TDF compared to the non-TDF group (1.9% vs. 4.0%). Among patients with no or mild renal dysfunction, those on TDF were more likely to develop moderate (adjusted OR: 3.11; 95%CI: 2.52-3.87) or severe eGFR decrease (adjusted OR: 2.43; 95%CI: 1.80-3.28), although the incidence of such episodes was low. Among patients with moderate or severe renal dysfunction at baseline, renal function improved independently of ART regimen and mortality was similar in both treatment groups. Conclusions. TDF use did not attenuate renal function recovery or increase mortality in patients with renal dysfunction. Further studies are needed to determine the role of routine renal function monitoring before and during ART use in Africa.

Landscape mosaics maps as a basis for spatial assessment and negotiation of ecosystem services and their trade-offs at the meso-scale: Examples from Laos, Madagascar and China

Mapping ecosystem services (ES) and their trade-offs is a key requirement for informed decision making for land use planning and management of natural resources that aim to move towards increasing the sustainability of landscapes. The negotiations of the purposes of landscapes and the services they should provide are difficult as there is an increasing number of stakeholders active at different levels with a variety of interests present on one particular landscape.Traditionally, land cover data is at the basis for mapping and spatial monitoring of ecosystem services. In light of complex landscapes it is however questionable whether land cover per se and as a spatial base unit is suitable for monitoring and management at the meso-scale. Often the characteristics of a landscape are defined by prevalence, composition and specific spatial and temporal patterns of different land cover types. The spatial delineation of shifting cultivation agriculture represents a prominent example of a land use system with its different land use intensities that requires alternative methodologies that go beyond the common remote sensing approaches of pixel-based land cover analysis due to the spatial and temporal dynamics of rotating cultivated and fallow fields.Against this background we advocate that adopting a landscape perspective to spatial planning and decision making offers new space for negotiation and collaboration, taking into account the needs of local resource users, and of the global community. For this purpose we introduce landscape mosaicsdefined as new spatial unit describing generalized land use types. Landscape mosaics have allowed us to chart different land use systems and land use intensities and permitted us to delineate changes in these land use systems based on changes of external claims on these landscapes. The underlying idea behindthe landscape mosaics is to use land cover data typically derived from remote sensing data and to analyse and classify spatial patterns of this land cover data using a moving window approach. We developed the landscape mosaics approach in tropical, forest dominated landscapesparticularly shifting cultivation areas and present examples ofour work from northern Laos, eastern Madagascarand Yunnan Province in China.