Prevention of mother-to-child transmission of HIV in Zambia: implementing efficacious ARV regimens in primary health centers

<p>Abstract</p> <p>Background</p> <p>Safety and effectiveness of efficacious antiretroviral (ARV) regimens beyond single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT) have been demonstrated in well-controlled clinical studies or in secondary- and tertiary-level facilities in developing countries. This paper reports on implementation of and factors associated with efficacious ARV regimens among HIV-positive pregnant women attending antenatal clinics in primary health centers (PHCs) in Zambia.</p> <p>Methods</p> <p>Blood sample taken for CD4 cell count, availability of CD4 count results, type of ARV prophylaxis for mothers, and additional PMTCT service data were collected for HIV-positive pregnant women and newborns who attended 60 PHCs between April 2007 and March 2008.</p> <p>Results</p> <p>Of 14,815 HIV-positive pregnant women registered in the 60 PHCs, 2,528 (17.1%) had their CD4 cells counted; of those, 1,680 (66.5%) had CD4 count results available at PHCs; of those, 796 (47.4%) had CD4 count ≤ 350 cells/mm³and thus were eligible for combination antiretroviral treatment (cART); and of those, 581 (73.0%) were initiated on cART. The proportion of HIV-positive pregnant women whose blood sample was collected for CD4 cell count was positively associated with (1) blood-draw for CD4 count occurring on the same day as determination of HIV-positive status; (2) CD4 results sent back to the health facilities within seven days; (3) facilities <it>without </it>providers trained to offer ART; and (4) urban location of PHC. Initiation of cART among HIV-positive pregnant women was associated with the PHC's capacity to provide care and antiretroviral treatment services. Overall, of the 14,815 HIV-positive pregnant women registered, 10,015 were initiated on any type of ARV regimen: 581 on cART, 3,041 on short course double ARV regimen, and 6,393 on sdNVP.</p> <p>Conclusion</p> <p>Efficacious ARV regimens beyond sdNVP can be implemented in resource-constrained PHCs. The majority (73.0%) of women identified eligible for ART were initiated on cART; however, a minority (11.3%) of HIV-positive pregnant women were assessed for CD4 count and had their test results available. Factors associated with implementation of more efficacious ARV regimens include timing of blood-draw for CD4 count and capacity to initiate cART onsite where PMTCT services were being offered.</p

Why the increase in under five mortality in Uganda from 1995 to 2000? A retrospective analysis

<p>Abstract</p> <p>Background</p> <p>From 1995-2000 the under five mortality rate in Uganda increased from 147.3 to 151.5 deaths per 1000 live births and reasons for the increase were not clear. This study was undertaken to understand factors influencing the increase in under five mortality rate during 1995-2000 in Uganda with a view of suggesting remedial actions.</p> <p>Methods</p> <p>We performed a comparative retrospective analysis of data derived from the 1995 and the 2000 Uganda demographic and health surveys. We correlated the change of under five mortality rate in Uganda desegregated by region (central, eastern, north and western) with change in major known determinants of under five mortality such social economic circumstances, maternal factors, access to health services, and level of nutrition.</p> <p>Results</p> <p>The increase in under five mortality rate only happened in western Uganda with the other 3 regions of Uganda (eastern, northern and central) showing a decrease. The changes in U5MR could not be explained by changes in poverty, maternal conditions, level of nutrition, or in access to health and other social services and in the prevalence of HIV among women attending for ante-natal care. All these factors did not reach statistical significance (P > 0.05) using Pearson's correlation coefficient.</p> <p>Conclusion</p> <p>In order to explain these findings, there is need to find something that happened in western Uganda (but not other parts of the country) during the period 1995-2000 and has the potential to change the under five mortality by a big margin. We hypothesize that the increase in under five mortality could be explained by the severe malaria epidemic that occurred in western Uganda (but not other regions) in 1997/98.</p

Health workers' views on quality of prevention of mother-to-child transmission and postnatal care for HIV-infected women and their children

<p>Abstract</p> <p>Background</p> <p>Prevention of mother-to-child transmission has been considered as not a simple intervention but a comprehensive set of interventions requiring capable health workers. Viet Nam's extensive health care system reaches the village level, but still HIV-infected mothers and children have received inadequate health care services for prevention of mother-to-child transmission. We report here the health workers' perceptions on factors that lead to their failure to give good quality prevention of mother-to-child transmission services.</p> <p>Methods</p> <p>Semistructured interviews with 53 health workers and unstructured observations in nine health facilities in Hanoi were conducted. Selection of respondents was based on their function, position and experience in the development or implementation of prevention of mother-to-child transmission policies/programmes.</p> <p>Results</p> <p>Factors that lead to health workers' failure to give good quality services for prevention of mother-to-child transmission include their own fear of HIV infection; lack of knowledge on HIV and counselling skills; or high workloads and lack of staff; unavailability of HIV testing at commune level; shortage of antiretroviral drugs; and lack of operational guidelines. A negative attitude during counselling and provision of care, treating in a separate area and avoidance of providing service at all were seen by health workers as the result of fear of being infected, as well as distrust towards almost all HIV-infected patients because of the prevailing association with antisocial behaviours. Additionally, the fragmentation of the health care system into specialized vertical pillars, including a vertical programme for HIV/AIDS, is a major obstacle to providing a continuum of care.</p> <p>Conclusion</p> <p>Many hospital staff were not being able to provide good care or were even unwilling to provide appropriate care for HIV-positive pregnant women The study suggests that the quality of prevention of mother-to-child transmission service could be enhanced by improving communication and other skills of health workers, providing them with greater support and enhancing their motivation. Reduction of workload would also be important. Development of a practical strategy is needed to strengthen and adapt the referral system to meet the needs of patients.</p

Amniotic fluid deficiency and congenital abnormalities both influence fluctuating asymmetry in developing limbs of human deceased fetuses

Fluctuating asymmetry (FA), as an indirect measure of developmental instability (DI), has been intensively studied for associations with stress and fitness. Patterns, however, appear heterogeneous and the underlying causes remain largely unknown. One aspect that has received relatively little attention in the literature is the consequence of direct mechanical effects on asymmetries. The crucial prerequisite for FA to reflect DI is that environmental conditions on both sides should be identical. This condition may be violated during early human development if amniotic fluid volume is deficient, as the resulting mechanical pressures may increase asymmetries. Indeed, we showed that limb bones of deceased human fetuses exhibited increased asymmetry, when there was not sufficient amniotic fluid (and, thus, space) in the uterine cavity. As amniotic fluid deficiency is known to cause substantial asymmetries and abnormal limb development, these subtle asymmetries are probably at least in part caused by the mechanical pressures. On the other hand, deficiencies in amniotic fluid volume are known to be associated with other congenital abnormalities that may disturb DI. More specifically, urogenital abnormalities can directly affect/reduce amniotic fluid volume. We disentangled the direct mechanical effects on FA from the indirect effects of urogenital abnormalities, the latter presumably representing DI. We discovered that both factors contributed significantly to the increase in FA. However, the direct mechanical effect of uterine pressure, albeit statistically significant, appeared less important than the effects of urogenital abnormalities, with an effect size only two-third as large. We, thus, conclude that correcting for the relevant direct factors allowed for a representative test of the association between DI and stress, and confirmed that fetuses form a suitable model system to increase our understanding in patterns of FA and symmetry development.Research Fund of the University of Antwerp, mobility grant from the Research Foundation – Flanders (FWO)

Estimation of HIV-1 incidence among five focal populations in Dehong, Yunnan: a hard hit area along a major drug trafficking route

<p>Abstract</p> <p>Background</p> <p>Since 1989 when the first 146 HIV positives in China were identified, Dehong Prefecture had been one of the areas hardest-hit by HIV in China. The local and national governments have put substantial financial resources into tackling the HIV epidemic in Dehong from 2004. The objective of this study was to track dynamic changes in HIV-1 prevalence and incidence among five focal populations in Dehong and to assess the impact of HIV prevention and control efforts.</p> <p>Methods</p> <p>Consecutive cross-sectional surveys conducted in five focal populations between 2004 and 2008. Specimens seropositive for HIV were tested with the BED IgG capture enzyme immunoassay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments.</p> <p>Results</p> <p>From 2004 to 2008, estimated annual HIV incidence among injecting drug users (IDUs) decreased significantly [from 15.0% (95% CI = 11.4%-18.5%) in 2004 to 4.3% (95% CI = 2.4%-6.2%) in 2008; trend test P < 0.0001]. The incidence among other focal populations, such as HIV discordant couples (varying from 5.5% to 4.7%), female sex workers (varying from 1.4% to 1.3%), pregnant women (0.1%), and pre-marital couples (0.2 to 0.1%) remained stable. Overall, the proportion of recent HIV-1 infections was higher among females than males (P < 0.0001).</p> <p>Conclusions</p> <p>The HIV epidemic in Dehong continued to expand during a five-year period but at a slowing rate among IDUs, and HIV incidence remains high among IDUs and discordant couples. Intensive prevention measures should target sub-groups at highest risk to further slow the epidemic and control the migration of HIV to other areas of China, and multivariate analysis is needed to explore which measures are more effective for different populations.</p

Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania

<p>Abstract</p> <p>Background</p> <p>HIV-associated anemia is common and associated with poor prognosis. However, its response to antiretroviral treatment (ART) in rural Africa is poorly understood.</p> <p>Methods</p> <p>HIV-infected adults (≥15 years) who enrolled in HIV care at Haydom Lutheran Hospital in northern Tanzania were included in the study. The effect of ART (zidovudine/stavudine + lamivudine + efavirenz/nevirapine) on HIV-associated anemia was studied in a subset of patients who were anemic at the time they started ART and had a follow-up hemoglobin measurement 12 months later. Pregnant women were excluded from the study, as were women who had given birth within the past 6 weeks. Anemia was defined as hemoglobin <12 g/dL in women and <13 g/dL in men. We applied paired sample T-tests to compare hemoglobin levels before and one year after ART initiation, and logistic regression models to identify predictors of persistent anemia.</p> <p>Results</p> <p>At enrollment, mean hemoglobin was 10.3 g/dL, and 649 of 838 patients (77.4%) were anemic. Of the anemic patients, 254 (39.1%) had microcytosis and hypochromia. Among 102 patients who were anemic at ART initiation and had a follow-up hemoglobin measurement after 12 months, the mean hemoglobin increased by 2.5 g/dL (<it>P </it>< 0.001); however, 39 patients (38.2%) were still anemic after 12 months of ART. Independent predictors of persistent anemia were mean cell volume in the lower quartile (<76.0 fL; Odds Ratio [OR] 4.34; 95% confidence interval [CI] 1.22-15.5) and a zidovudine-containing initial regimen (OR 2.91; 95% CI 1.03-8.19).</p> <p>Conclusions</p> <p>Most patients had anemia at enrollment, of whom nearly 40% had microcytosis and hypochromia suggestive of iron deficiency. The mean hemoglobin increased significantly in patients who received ART, but one third were still anemic 12 months after ART initiation indicating that additional interventions to treat HIV-associated anemia in rural Africa might be warranted, particularly in patients with microcytosis and those treated with zidovudine.</p

Who is to blame? Perspectives of caregivers on barriers to accessing healthcare for the under-fives in Butere District, Western Kenya

<p>Abstract</p> <p>Background</p> <p>Kenya, like many developing nations, continues to experience high childhood mortality in spite of the many efforts put in place by governments and international bodies to curb it. This study sought to investigate the barriers to accessing healthcare services for children aged less than five years in Butere District, a rural district experiencing high rates of mortality and morbidity despite having relatively better conditions for child survival.</p> <p>Methods</p> <p>Exit interviews were conducted among caregivers seeking healthcare for their children in mid 2007 in all the 6 public health facilities. Additionally, views from caregivers in the community, health workers and district health managers were sought through focus group discussions (FGDs) and key informant interviews (KIs).</p> <p>Results</p> <p>Three hundred and ninety-seven respondents were surveyed in exit interviews while 45 respondents participated in FGDs and KIs. Some practices by caregivers including early onset of child bearing, early supplementation, and utilization of traditional healers were thought to increase the risk of mortality and morbidity, although reported rates of mosquito net utilization and immunization coverage were high. The healthcare system posed barriers to access of healthcare for the under fives, through long waiting time, lack of drugs and poor services, incompetence and perceived poor attitudes of the health workers. FGDs also revealed wide-spread concerns and misconceptions about health care among the caregivers.</p> <p>Conclusion</p> <p>Caregivers' actions were thought to influence children's progression to illness or health while the healthcare delivery system posed recurrent barriers to the accessing of healthcare for the under-fives. Actions on both fronts are necessary to reduce childhood mortality.</p

Determinants for HIV testing and counselling in Nairobi urban informal settlements

BACKGROUND: Counselling and testing is important in HIV prevention and care. Majority of people in sub-Saharan Africa do not know their HIV status and are therefore unable to take steps to prevent infection or take up life prolonging anti-retroviral drugs in time if infected. This study aimed at exploring determinants of HIV testing and counselling in two Nairobi informal settlements. METHODS: Data are derived from a cross-sectional survey nested in an ongoing demographic surveillance system. A total of 3,162 individuals responded to the interview and out of these, 82% provided a blood sample which was tested using rapid test kits. The outcome of interest in this paper was HIV testing status in the past categorised as "never tested"; "client-initiated testing and counselling (CITC)" and provider-initiated testing and counselling (PITC). Multinomial logistic regression was used to identify determinants of HIV testing. RESULTS: Approximately 31% of all respondents had ever been tested for HIV through CITC, 22% through PITC and 42% had never been tested but indicated willingness to test. Overall, 62% of females and 38% of males had ever been tested for HIV. Males were less likely to have had CITC (OR = 0.47; p value < 0.001) and also less likely to have had PITC (OR = 0.16; p value < 0.001) compared to females. Individuals aged 20-24 years were more likely to have had either CITC or PITC compared to the other age groups. The divorced/separated/widowed were more likely (OR = 1.65; p value < 0.01) to have had CITC than their married counterparts, while the never married were less likely to have had either CITC or PITC. HIV positive individuals (OR = 1.60; p value < 0.01) and those who refused testing in the survey (OR = 1.39; p value < 0.05) were more likely to have had CITC compared to their HIV negative counterparts. CONCLUSION: Although the proportion of individuals ever tested in the informal settlements is similar to the national average, it remains low compared to that of Nairobi province especially among men. Key determinants of HIV testing and counselling include; gender, age, education level, HIV status and marital status. These factors need to be considered in efforts aimed at increasing participation in HIV testing

Women experience a better long-term immune recovery and a better survival on HAART in Lao People's Democratic Republic.

<p>Abstract</p> <p>Background</p> <p>In April 2003, Médecins Sans Frontières launched an HIV/AIDS programme to provide free HAART to HIV-infected patients in Laos. Although HIV prevalence is estimated as low in this country, it has been increasing in the last years. This work reports the first results of an observational cohort study and it aims to identify the principal determinants of the CD4 cells evolution and to assess mortality among patients on HAART.</p> <p>Methods</p> <p>We performed a retrospective database analysis on patients initiated on HAART between 2003 and 2009 (CD4<200cells/μL or WHO stage 4). We excluded from the analysis patients who were less than 16 years old and pregnant women. To explore the determinants of the CD4 reconstitution, a linear mixed model was adjusted. To identify typical trajectories of the CD4 cells, a latent trajectory analysis was carried out. Finally, a Cox proportional-hazards model was used to reveal predictors of mortality on HAART including appointment delay greater than 1 day.</p> <p>Results</p> <p>A total of 1365 patients entered the programme and 913 (66.9%) received an HAART with a median CD4 of 49 cells/μL [IQR 15–148]. High baseline CD4 cell count and female gender were associated with a higher CD4 level over time. In addition, this gender difference increased over time. Two typical latent CD4 trajectories were revealed showing that 31% of women against 22% of men followed a high CD4 trajectory. In the long-term, women were more likely to attend appointments without delay. Mortality reached 6.2% (95% CI 4.8-8.0%) at 4 months and 9.1% (95% CI 7.3-11.3%) at 1 year. Female gender (HR=0.17, 95% CI 0.07-0.44) and high CD4 trajectory (HR=0.19, 95% CI 0.08-0.47) were independently associated with a lower death rate.</p> <p>Conclusions</p> <p>Patients who initiated HAART were severely immunocompromised yielding to a high early mortality. In the long-term on HAART, women achieved a better CD4 cells reconstitution than men and were less likely to die. This study highlights important differences between men and women regarding response to HAART and medical care, and questions men’s compliance to treatment.</p

Cyclic di-GMP is Essential for the Survival of the Lyme Disease Spirochete in Ticks

Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host