Retention in a NGO supported antiretroviral program in the Democratic Republic of Congo.

BACKGROUND: Retention of patients in ART care is a major challenge in sub-Saharan programs. Retention is also one of the key indicators to evaluate the success of ART programs. METHODS AND FINDINGS: A retrospective review of 1500 randomly selected medical charts of adult ART patients from a local non-governmental (NGO) supported ART program in the Democratic Republic of Congo (DRC). Retention was defined as any visit to the clinic in the 4 months prior to the abstraction date. Retention over time and across different sites was described. The relationship between patient characteristics and retention rates at 1 year was also examined. 1450 patients were included in the analysis. The overall retention rates were 81.4% (95% CI: 79.3-83.4), 75.2% (95% CI: 72.8-77.3), 65.0% (95% CI: 62.3-67.6) and 57.2% (95% CI: 54.0-60.3) at 6 months, 1 year, 2 years and 3 years respectively. The retention rates between sites varied between 62.1% and 90.6% at 6 months and between 55.5% and 86.2% at 1 year. During multivariable analysis weight below 50 kg (aHR: 1.33, 95%CI: 1.05-1.69), higher WHO stage at initiation (aHR: 1.22, 95%CI 0.85-1.76 for stage 3 and aHR: 2.98, 95%CI: 1.93-4.59 for stage 4), and male sex (aHR: 1.32, 95%CI: 1.05-1.65) remained as significant risk factors for attrition during the first year after ART initiation. Other independent risk factors were year of initiation (aHR: 1.73, 95%CI: 1.26-2.38 for the year 2007 and aHR: 3.06, 95%CI: 2.26-4.14 for the period 2008-2009), and site. CONCLUSIONS: Retention is a major problem in DRC, while coverage of patients on ART is still very low. With the flattening of funding for HIV care and treatment in sub-Saharan Africa, and with decreasing funding worldwide, maximizing retention during the much needed scaling-up will even be more important.

Cancer care challenges in developing countries.

BACKGROUND: Health systems in Sub-Saharan Africa are not prepared for the rapid rise in cancer rates projected in the region over the next decades. More must be understood about the current state of cancer care in this region to target improvement efforts. Yaounde General Hospital (YGH) currently is the only site in Cameroon (population: 18.8 million) where adults can receive chemotherapy from trained medical oncologists. The experiences of patients at this facility represent a useful paradigm for describing cancer care in this region. METHODS: In July and August 2010, our multidisciplinary team conducted closed-end interviews with 79 consecutive patients who had confirmed breast cancer, Kaposi sarcoma, or lymphoma. RESULTS: Thirty-five percent of patients waited >6 months to speak to a health care provider after the first sign of their cancer. The delay between first consultation with a health care provider and receipt of a cancer diagnosis was >3 months for 47% of patients. The total delay from the first sign of cancer to receipt of the correct diagnosis was >6 months for 63% of patients. Twenty-three percent of patients traveled for >7 hours to reach YGH, and 40% of patients interviewed spent >$200 on a single round of chemotherapy. CONCLUSIONS: Cancer patients experienced numerous geographic and health care system challenges, resulting in significant delays in receiving diagnosis and treatment, even for cancers highly amenable to early intervention. This unacceptable and unethical situation is likely explained by limited knowledge about cancer among patients and health care professionals, government neglect, poverty, and reliance on traditional healers.

Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria.

BACKGROUND: The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, such as artesunate (AS), are poorly understood. In this analysis, the population pharmacokinetics of oral AS, and its active metabolite dihydroartemisinin (DHA), were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC. METHODS: Data were obtained from 26 pregnant women in the second (22-26 weeks) or the third (32-36 weeks) trimester of pregnancy and from 25 non-pregnant female controls. All subjects received 200 mg AS. Plasma AS and DHA were measured using a validated LC-MS method. Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling. RESULTS: A simultaneous parent-metabolite model was developed consisting of mixed zero-order, lagged first-order absorption of AS, a one-compartment model for AS, and a one-compartment model for DHA. Complete conversion of AS to DHA was assumed. The model displayed satisfactory goodness-of-fit, stability, and predictive ability. Apparent clearance (CL/F) and volume of distribution (V/F) estimates, with 95% bootstrap confidence intervals, were as follows: 195 L (139-285 L) for AS V/F, 895 L/h (788-1045 L/h) for AS CL/F, 91.4 L (78.5-109 L) for DHA V/F, and 64.0 L/h (55.1-75.2 L/h) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant, with a pregnancy-associated increase in DHA CL/F of 42.3% (19.7-72.3%). CONCLUSIONS: In this analysis, pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS. These findings, in conjunction with a previous non-compartmental analysis of the modelled data, provide further evidence that higher AS doses would be required to maintain similar DHA levels in pregnant women as achieved in non-pregnant controls.

Pharmacokinetics and pharmacodynamics of artesunate and dihydroartemisinin following oral treatment in pregnant women with asymptomatic Plasmodium falciparum infections in Kinshasa DRC.

BACKGROUND: In many malaria-endemic countries, increasing resistance may soon compromise the efficacy of sulphadoxine-pyrimethamine (SP) for intermittent preventative treatment (IPT) of malaria in pregnancy. Artemisinin-based IPT regimens represent a promising potential alternative to SP. Pharmacokinetic and safety data supporting the use of artemisinin derivatives in pregnancy are urgently needed. METHODS: Subjects included pregnant women with asymptomatic falciparum parasitaemia between 22-26 weeks (n = 13) or 32-36 weeks gestation (n = 13), the same women at three months postpartum, and 25 non-pregnant parasitaemic controls. All subjects received 200 mg orally administered AS. Plasma total and free levels of AS and its active metabolite DHA were determined using a validated LC-MS method. Non-compartmental pharmacokinetic analysis was performed using standard methods. RESULTS: All pregnant women delivered live babies. The median birth weight was 3025 grams [range 2130, 3620]; 2 of 26 babies had birth weights less than 2500 grams. Rates of parasite clearance by 12 hours post-dose were high and comparable among the groups. Rapid elimination of AS was observed in all three groups. The 90% CI for the pregnancy:postpartum ratio of geometric means for total and free AUC fell within the pre-specified 0.66 - 1.50 therapeutic equivalence interval. However, more pronounced pharmacokinetic differences were observed between the pregnancy and control subjects, with the 90% CI for the pregnancy:control ratio of geometric means for both total 0.68 (90% CI 0.57-0.81) and free AUC 0.78 (90% CI 0.63-0.95) not fully contained within the 0.66 - 1.50 interval. All subjects cleared parasites rapidly, and there was no difference in the percentage of women who were parasitaemic 12 hours after dosing. CONCLUSIONS: A single dose of orally administered AS was found to be both effective and without adverse effects in this study of second and third trimester pregnant women in the DRC. Although DHA AUC during pregnancy and postpartum were similar, the AUC for the pregnant group was less than the non-pregnant controls. The findings of this study suggest that additional studies on the pharmacokinetics of AS in pregnant women are needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00538382.

Local differences in human immunodeficiency virus prevalence: a comparison of social venue patrons, antenatal patients, and sexually transmitted infection patients in eastern kinshasa.

BACKGROUND: This study compares the sexual behavior and HIV prevalence of men and women at social venues where people meet new sexual partners in Eastern Kinshasa with that of sexually transmitted infection (STI) treatment and antenatal clinic (ANC) patients in the same area. METHODS: ANC patients, STI clinic patients, and social venue patrons were interviewed, asked to provide a blood sample on-site, and provided with information about obtaining test results. Every patron at identified social venues in the study area was invited to participate. RESULTS: One thousand one hundred sixteen pregnant women; 66 male and 229 female STI clinic patients; and 952 male and 247 female patrons of social venues were interviewed and tested for HIV. HIV prevalence differed by group: ANC patients (4%); female venue patrons (12%); female STI patients (16%); male venue patrons (2%); and male STI patients (23%). HIV prevalence among sex workers at social venues (29%) was higher than HIV prevalence among other female patrons with new or multiple partnerships in the past four weeks (19%) and higher than HIV prevalence among female patrons denying sex work (6%). However, the absolute number of infected women was higher among women reporting recent new or multiple partnerships than among the smaller group of sex workers (23 vs. 18). Two-thirds of the infected female STI patients (24/36) reported no more than one and no new sexual partner in the past year. CONCLUSION: Improving prevention programs in Kinshasa is essential. Prevention efforts should not neglect women at social venues who do not self-identify as sex workers but who have high rates of new sexual partnership formation.

Post-partum depression in Kinshasa, Democratic Republic of Congo: validation of a concept using a mixed-methods cross-cultural approach.

OBJECTIVE: To determine if a post-partum depression syndrome exists among mothers in Kinshasa, Democratic Republic of Congo, by adapting and validating standard screening instruments. METHODS: Using qualitative interviewing techniques, we interviewed a convenience sample of 80 women living in a large peri-urban community to better understand local conceptions of mental illness. We used this information to adapt two standard depression screeners, the Edinburgh Post-partum Depression Scale and the Hopkins Symptom Checklist. In a subsequent quantitative study, we identified another 133 women with and without the local depression syndrome and used this information to validate the adapted screening instruments. RESULTS: Based on the qualitative data, we found a local syndrome that closely approximates the Western model of major depressive disorder. The women we interviewed, representative of the local populace, considered this an important syndrome among new mothers because it negatively affects women and their young children. Women (n = 41) identified as suffering from this syndrome had statistically significantly higher depression severity scores on both adapted screeners than women identified as not having this syndrome (n = 20; P < 0.0001). CONCLUSIONS: When it is unclear or unknown if Western models of psychopathology are appropriate for use in the local context, these models must be validated to ensure cross-cultural applicability. Using a mixed-methods approach we found a local syndrome similar to depression and validated instruments to screen for this disorder. As the importance of compromised mental health in developing world populations becomes recognized, the methods described in this report will be useful more widely.

Endemic human monkeypox, Democratic Republic of Congo, 2001-2004.

By analyzing vesicle fluids and crusted scabs from 136 persons with suspected monkeypox, we identified 51 cases of monkeypox by PCR, sequenced the hemagglutinin gene, and confirmed 94% of cases by virus culture. PCR demonstrated chickenpox in 61 patients. Coinfection with both viruses was found in 1 additional patient.

The rate of epidemiological and virological changes during the transition from nascent to concentrated HIV epidemic stage in the former Soviet Union countries.

The rate of processes accompanying the transition of the HIV-1 epidemic from nascent stage to concentrated one in the Former Soviet Union (FSU) during intravenous drug user (IDU)-associated HIV infection outbreaks in 1994-1999 has not been analyzed. To define the rates, we studied susceptible populations and circulating viruses before, during, and after the outbreaks. Our findings included the following: (1) the pattern of high HIV-1 genetic diversity characteristic of the nascent epidemic changed to a concentrated one within 1 year in St. Petersburg and in Moscow; (2) different FSU regions were at different stages of the HIV-1 epidemic in 1994-1996; (3) the change of serotypic patterns characteristic of different stages of the HIV/AIDS epidemic for the non-IDU risk group occurred within 1 year in Moscow, suggesting an extremely high rate of IDU-associated epidemic pattern distributions in regions and susceptible populations in the FSU.

HIV prevalence, sociodemographic, and behavioral correlates and recruitment methods among injection drug users in St. Petersburg, Russia.

OBJECTIVE: In St. Petersburg, Russia, we sought to describe the characteristics of active high-risk injection drug users (IDUs) to evaluate the associations between behavioral and demographic characteristics and HIV-1 infection and to describe 3 discrete recruitment methods. METHODS: Active high-risk IDUs were recruited in 3 ways: through street outreach, at facilities serving IDUs, and by network-based chain referral. Recruits were screened, counseled, and tested for HIV-1. Sociodemographic and behavioral data were collected. HIV-1 prevalence was analyzed as a function of sociodemographic and behavioral variables. RESULTS: During the 10-month recruitment period, data from 900 participants were collected: median age was 24 years, and in the previous month, 96% used heroin and 75% shared needles with others. The baseline HIV prevalence was 30% (95% confidence interval [CI]: 27 to 33). Recruitment through social networks was the most productive strategy. HIV-positive individuals were younger, but none of the other sociodemographic or behavioral characteristics differed significantly by HIV status. CONCLUSIONS: The estimated HIV prevalence of 30% places St. Petersburg among the worst IDU-concentrated epidemics in Europe. Recruitment through network-based chain referral is a useful method for recruiting active IDUs. Sociodemographic and behavioral links to prevalent HIV infection remain to be elucidated.

HIV incidence and factors associated with HIV acquisition among injection drug users in St Petersburg, Russia.

BACKGROUND: The Russian HIV-1 epidemic has been driven by injection drug use. OBJECTIVE: To determine HIV incidence and identify demographic and behavioral correlates of infection to facilitate the development of longitudinal HIV prevention programs. METHODS: In 2002, a cohort of 520 injection drug users (IDU) in St Petersburg, Russia were recruited and tested and counseled for HIV-1. HIV-seronegative IDU were enrolled and reevaluated at 6 and 12 months. HIV testing was performed and sociodemographic and behavioral data were collected during each study visit. The relationship of sociodemographic and behavioral factors to HIV-1 incidence was assessed. RESULTS: Most enrolled subjects were young, male, living at home, educated, heroin users, and frequently shared needles and other injection paraphernalia. The retention rate at the 12 month follow-up was 80%. The HIV-1 incidence rate was 4.5/100 person-years. In univariate analysis, psychostimulant use, especially frequent use, three or more sex partners in the past 6 months, and females selling sex were associated with HIV seroconversion. In the multivariate analysis, psychostimulant use three or more times per week was the only factor still associated with HIV seroconversion. CONCLUSIONS: The high incidence of HIV infection places St Petersburg among the worst IDU-concentrated epidemics in Europe. Interventions targeting psychostimulant and heroin users and their accompanying behaviors such as frequent injections and increased sexual activity are needed immediately.

Syphilis management in St. Petersburg, Russia: 1995-2001.

OBJECTIVES: The objectives of this study were to describe the recent syphilis epidemic in St. Petersburg, Russia; and to document the syphilis management practices in Russia to help inform the best way forward for a system in transition. DESIGN: This study was a retrospective cohort study of syphilis diagnosed and followed in St. Petersburg, 1995-2001. RESULTS: A total of 1,024 persons were identified with syphilis. Persons treated for secondary syphilis with 400,000 IU aqueous penicillin intramuscularly every 3 hours for 28 days or 2.4 micro benzathine penicillin intramuscularly weekly for 2 weeks responded most rapidly. Persons treated with 1.5 micro bicillin-5 intramuscularly at diagnosis and then two times per week for 3 weeks or 2.4 micro bicillin-1 intramuscularly weekly for 3 weeks displayed sluggish responses (P<0.0001). Regimens for treating later stages revealed similar responses (P=0.21). Benzathine penicillin at a dosage of 2.4 micro intramuscularly weekly for 3 weeks was not a used regimen. CONCLUSION: Benzathine penicillin at a dosage of 2.4 mu intramuscularly weekly for 1 to 2 weeks is in moderate use but its use should increase; 2.4 mu benzathine penicillin intramuscularly weekly for 3 weeks should be introduced as the standard of care for late syphilis. The efficacy of the locally manufactured bicillin-1 and bicillin-5 is in question.

Validation of a brief screening instrument for substance abuse and mental illness in HIV-positive patients.

BACKGROUND: Substance abuse (SA) and mental illness (MI) commonly co-occur with HIV infection in the United States and have important implications for clinical management of HIV/AIDS. Yet SA/MI often go untreated due in part to a lack of practical, validated screening tools. SETTING: HIV clinic in academic medical center. METHODS: The 16-item SA/MI Symptoms Screener (SAMISS) targets SA/MI in HIV-positive patients. Consecutive consenting HIV-positive patients completed the SAMISS and then a reference standard diagnostic tool, SCID, the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). RESULTS: Twenty percent of participants (29/148) had an SA diagnosis and 41% (59/143) had an MI diagnosis in the past year on the SCID; 48% (68/143) had 1 or both. Thirty-seven percent (55/148) screened positive for SA and 69% (99/143) screened positive for MI on the SAMISS. The SAMISS had 86% (95% CI: 68%-96%) sensitivity and 75% (66%-82%) specificity for SA and 95% (86%-99%) sensitivity and 49% (38%-60%) specificity for MI. Patients with SA were likely to show up as false positives for MI and vice versa. CONCLUSION: The SAMISS functioned well as a first-line screening tool for SA/MI in this HIV clinic population. It missed few cases and was easily incorporated into a busy clinical setting. Persons screening positive require a more rigorous confirmatory psychiatric evaluation.

Low seroprevalence of IgG antibodies to Ebola virus in an epidemic zone: Ogooué-Ivindo region, Northeastern Gabon, 1997.

A population-based serosurvey was performed to determine the seroprevalence of antibodies to Ebola virus (EBO) in a region that has experienced multiple epidemics of EBO hemorrhagic fever. Of 2533 residents in 8 villages, serum samples from 979 (38.6%) were tested by enzyme-linked immunosorbent assay for immunoglobulin (Ig) G and IgM antibodies to Ebola-Zaire (EBO-Z) virus. Fourteen samples (1.4%) were found positive for IgG antibodies, and 4 of these (.4%) were samples from survivors of an epidemic of EBO hemorrhagic fever. Seroprevalence based on the remaining 10 IgG-seropositive individuals with no history of exposure to EBO was 1.0% (exact binomial 95% confidence interval, 0.5%-1.9%). No serum samples were found positive for IgM antibodies to EBO-Z virus. The low seroprevalence suggests that, outside of recognized outbreaks, human exposure to EBO in this epidemic zone is rare.

A comparison of height and weight velocity as a part of the composite endpoint in pediatric HIV.

BACKGROUND: HIV adversely affects growth in children. Pediatric AIDS Clinical Trial Group (PACTG) protocols often use weight velocity [changes in weight z-score for age (WAZ)] as a part of the composite endpoint for phase II and III clinical trials. However, WAZ and height velocity (HAZ) have not been critically compared for their utility as part of the composite endpoint. METHODS: HAZ and WAZ were compared to predict laboratory and clinical progression of HIV in a retrospective cohort study of HIV-infected children with data from PACTG Protocol 300. RESULTS: In both bivariable and multivariable analyses, changes in HAZ were more closely linked to subsequent progression than WAZ. Children with improved HAZ were somewhat less likely to exhibit virological failure [odds ratio (OR), 0.76; 95% confidence interval (CI) 0.51-1.14], than children with improved WAZ (OR, 1.45; 95% CI, 0.99,2.11). Children who had improved HAZ were less likely to exhibit immunological failure (OR, 0.7; 95% CI, 0.49-1.00), than children with improved WAZ (OR, 1.13; 95% CI, 0.82-1.57). Children who had improved HAZ were less likely to have other forms of clinical progression of HIV (OR, 0.55; 95% CI, 0.31-0.99), than children who had improved WAZ (OR, 1.0; 95% CI, 1.58-1.94). CONCLUSIONS: Increases in HAZ were associated with reduced risk of subsequent clinical progression and subsequent immune reconstitution and weakly associated with declines in HIV RNA. Changes in WAZ were not associated with laboratory outcomes relevant to pediatric HIV infection. Height velocity should be considered as a component of a composite clinical endpoint in future PACTG trials.

Tick-borne encephalitis with hemorrhagic syndrome, Novosibirsk region, Russia, 1999.

Eight fatal cases of tick-borne encephalitis with an unusual hemorrhagic syndrome were identified in 1999 in the Novosibirsk Region, Russia. To study these strains, we sequenced cDNA fragments of protein E gene from six archival formalin-fixed brain samples. Phylogenetic analysis showed tick-borne encephalitis variants clustered with a Far Eastern subtype (homology 94.7%) but not with the Siberian subtype (82%).

Search for reiter's syndrome after an outbreak of shigella sonnei dysentery

Forty-seven percent of 4,205 individuals living in a Puerto-Rican community developed shigella sonnei dysentery. Questionnaire and, where relevant, clinical evaluation of 1,970 patients and the remaining 2,235 unaffected residents disclosed no cases of reiter's syndrome (RS). Among the possible explanations for failure to observe any cases is the important suggestion that s. sonnei is not arthritogenic (AU)