Alash’le Abimiku

Laboratory Diagnosis of Tuberculosis in Resource-Poor Countries: Challenges and Opportunities

SUMMARY With an estimated 9.4 million new cases globally, tuberculosis (TB) continues to be a major public health concern. Eighty percent of all cases worldwide occur in 22 high-burden, mainly resource-poor settings. This devastating impact of tuberculosis on vulnerable populations is also driven by its deadly synergy with HIV. Therefore, building capacity and enhancing universal access to rapid and accurate laboratory diagnostics are necessary to control TB and HIV-TB coinfections in resource-limited countries. The present review describes several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in such countries. Recently, the WHO has endorsed some of these novel methods, and they have been made available at discounted prices for procurement by the public health sector of high-burden countries. In addition, international and national laboratory partners and donors are currently evaluating other new diagnostics that will allow further and more rapid testing in point-of-care settings. While some techniques are simple, others have complex requirements, and therefore, it is important to carefully determine how to link these new tests and incorporate them within a countrys national diagnostic algorithm. Finally, the successful implementation of these methods is dependent on key partnerships in the international laboratory community and ensuring that adequate quality assurance programs are inherent in each countrys laboratory network.

Viremia control following antiretroviral treatment and therapeutic immunizationduring primary SIV 251 infection of macaques

Prolonged antiretroviral therapy (ART) is not likely to eradicate human immunodeficiency virus type I (HIV-I) infection. Here we explore the effect of therapeutic immunization in the context of ART during primary infection using the simian immunodeficiency virus (SIV251) macaque model. Vaccination of rhesus macaques with the highly attenuated poxvirus-based NYVAC-SIV vaccine expressing structural genes elicited vigorous virus-specific CD4+ and CD8+ T cell responses in macaques that responded effectively to ART. Following discontinuation of a six-month ART regimen, viral rebound occurred in most animals, but was transient in six of eight vaccinated animals. Viral rebound was also transient in four of seven mock-vaccinated control animals. These data establish the importance of antiretroviral treatment during primary infection and demonstrate that virus-specific immune responses in the infected host can be expanded by therapeutic immunization.

Patient Retention and Adherence to Antiretrovirals in a Large Antiretroviral Therapy Program in Nigeria: A Longitudinal Analysis for Risk Factors

Background Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART) and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU) and non-adherence to ART in a large treatment cohort in Nigeria. Methods and Findings We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE) regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p<0.001), post-secondary education (p = 0.03), and initiating treatment with zidovudine-containing (p = 0.004) or tenofovir-containing (p = 0.05) regimens were associated with decreased risk of LTFU, while patients with only primary education (p = 0.02) and those with baseline CD4 counts (cell/ml3) >350 and <100 were at a higher risk of LTFU compared to patients with baseline CD4 counts of 100–200. The adjusted GEE analysis showed that patients aged <35 years (p = 0.005), who traveled for >2 hours to the clinic (p = 0.03), had total ART duration of >6 months (p<0.001), and CD4 counts >200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01) and were treated with tenofovir-containing regimens (p≤0.001) were more likely to be adherent. Conclusions These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence.

Prevalence of non-tuberculous mycobacterial infections among tuberculosis suspects in Nigeria.

Background Nigeria is ranked in the top five countries for tuberculosis deaths worldwide. This study investigated the mycobacterial agents associated with presumptive clinical pulmonary tuberculosis (TB) in Nigeria and evaluated the pattern and frequency of mycobacterial infections over twelve calendar months period. Methods Sputum samples from 1,603 consecutive new cases with presumptive diagnosis of TB were collected from August 2010 to July 2011. All sputum samples were incubated for detection of mycobacterial growth and those with positive acid fast bacilli (AFB) growth were tested to detect mycobacterium tuberculosis (MTB) complex and characterized to differentiate between MTB complex species. Cultures suggestive of Non-tuberculous mycobacterial infections (NTM) were sub-cultured and characterized. Results Of the 1,603 patients screened, 444 (28%) culture-positive cases of pulmonary tuberculosis were identified. Of these, 375 (85%) were due to strains of MTB complex (354 cases of M. tuberculosis, 20 M. africanum and one case of M. bovis) and 69 (15%) were due to infection with NTM. In contrast to the MTB complex cases, the NTM cases were more likely to have been diagnosed during the calendar months of the Harmattan dust season (OR = 2.34, 1.28–4.29; p = 0.01), and aged older than 35 years (OR = 2.77, 1.52–5.02, p = 0.0007), but less likely to have AFB identified on their sputum smear (OR = 0.06, 0.02–0.14, p<0.0001). Among those with NTM infection, cases 35 years or younger were more likely to have co-infection with HIV (3.76, 1.72–8.22; p = 0.0009) compared to those older than 35 years. Interpretation The high proportion of younger patients with clinical pulmonary TB due to NTM and co-infection with HIV and the likely role of the seasonal dust exposure in the occurrence of the disease, present novel public health challenges for prevention and treatment.

Reference Values of CD4 T Lymphocytes in Human Immunodeficiency Virus-Negative Adult Nigerians

ABSTRACT A cross-sectional study that involved secondary analysis of data collected from 681 pregnant women and 183 miners (94 men and 89 women; ratio of men to women, 1:0.95) in Jos, Nigeria, was carried out to determine the reference ranges for CD4+-cell counts in healthy HIV-negative adult Nigerians. The main results of interest were CD4+-cell counts and odds ratios (ORs) of low CD4+-cell counts, defined as below 350 cells per μl. CD4+-cell counts were similar in men and nonpregnant women, with a mean (standard deviation) of 828 (203) cells per μl, but pregnant women had a lower value of 771 (250) cells per μl. None of the factors assessed was related to the odds of having a low CD4+-cell count among men and nonpregnant women, but age, age of marriage, and alcohol usage were significant predictors in pregnant women. Compared to pregnant women less than 20 years old, older women had significantly lower odds of a low CD4+-cell count (ORs were 0.06 for women aged 20 to 29 years and 0.22 for those aged 30 to 39 years). When compared with those pregnant women who were married before 20 years of age, those who married at 20 to 29 years and 30 to 39 years had odds ratios of 6.41 and 9.40, respectively. Previous alcohol use was also associated with low CD4+-cell counts (OR, 5.15). The 95% confidence interval for CD4+-cell counts in healthy adult Nigerians is 547 to 1,327 cells per μl, and this is the first time this has been determined.

Building Laboratory Infrastructure to Support Scale-Up of HIV/AIDS Treatment, Care, and Prevention: In-Country Experience

An unprecedented influx of funds and support through large programs such as the Global Fund for AIDS, Malaria and Tuberculosis and the World Health Organizations and Presidents Emergency Plan for AIDS Relief (PEPFAR) has made it possible for more than 1 million persons in resource-limited settings to access AIDS treatment and several million more to be in care and prevention programs. Nevertheless, there remain major challenges that prevent AIDS drugs and care from reaching many more in need, especially in rural settings. The roll-out of a high-quality treatment, care, and prevention program depends on an effective and reliable laboratory infrastructure. This article presents a strategy used by the Institute of Human Virology (IHV)-University of Maryland and its affiliate IHV-Nigeria to establish a multifaceted, integrated tier laboratory program to support a PEPFAR-funded scale-up of its AIDS Care Treatment in Nigeria program, in collaboration with the Centers for Disease Control and Prevention and the Nigerian government, as a possible model for overcoming a key challenge that faces several resource-limited countries trying to roll out and scale-up their HIV/AIDS treatment, care, and prevention program.

Immuno-virologic outcomes and immuno-virologic discordance among adults alive and on anti-retroviral therapy at 12 months in Nigeria

BackgroundPredictors of immuno-virologic outcomes and discordance and their associations with clinical, demographic, socio-economic and behavioral risk factors are not well described in Nigeria since HIV viral load testing is not routinely offered in public HIV treatment programs.MethodsThe HACART study was a multi-center observational clinic-based cohort study of 2585 adults who started HAART between April 2008 and February 2009. A total of 628 patients were randomly selected at 12 months for immuno-virologic analyses.ResultsVirologic suppression rate (<400 copies/ml) was 76.7%, immunologic recovery rate (CD4 change from baseline ≥50 cells/mm3) was 77.4% and immuno-virologic discordance rate was 33%. In multivariate logistic regression, virologic failure was associated with age <30 years (OR 1.79; 95% CI: 1.17-2.67, p=0.03), anemia (Hemoglobin < 10 g/dl) (OR 1.71; 95% CI: 1.22-2.61, p=0.03), poor adherence (OR 3.82; 95% CI: 2.17-5.97, p=0.001), and post-secondary education (OR 0.60; 95% CI: 0.30-0.86, p=0.02). Immunologic failure was associated with male gender (OR 1.46; 95% CI: 1.04-2.45, p=0.04), and age <30 years (OR 1.50; 95% CI: 1.11-2.39, p=0.03). Virologic failure with immunologic success (VL-/CD4+) was associated with anemia (OR 1.80; 95% CI: 1.13-2.88, p=0.03), poor adherence (OR 3.90; 95% CI: 1.92-8.24, p=0.001), and post-secondary education (OR 0.40; 95% CI: 0.22-0.68, p=0.005).ConclusionsAlthough favorable immuno-virologic outcomes could be achieved in this large ART program, immuno-virologic discordance was observed in a third of the patients. Focusing on intensified treatment preparation and adherence, young patients, males, persons with low educational status and most importantly baseline anemia assessment and management may help address predictors of poor immuno-virologic outcomes, and improve overall HIV program impact. Viral load testing in addition to the CD4 testing should be considered to identify, characterize and address negative immuno-virologic outcomes and discordance.

Social determinants of mixed feeding behavior among HIV-infected mothers in Jos, Nigeria

Abstract Mixed feeding confers excess risk of mother-to-child transmission (MTCT) of HIV compared with exclusive breastfeeding and exclusive formula feeding. We undertook a qualitative and quantitative cross-sectional survey to identify the social determinants of mixed feeding among a subset of the 469 HIV-infected women enrolled in a MTCT prevention program in Jos, Nigeria. Formula was provided free-of-cost. Of the 91 participants, 68 (75%) exclusively formula fed, 7 (8%) exclusively breastfed, and 16 (18%) practiced mixed feeding. Of the mixed feeding women, seven primarily formula fed and nine primarily breastfed. Women who primarily formula fed described family pressure as the reason for mixed feeding, while women who primarily breastfed reported insufficient breast milk. In a multivariate analysis, lack of partner support of the feeding decision predicted mixed feeding behavior (OR: 4.2; 95% CI: 1.2–14.9; p=0.03). Disclosure of HIV status was significantly correlated (p<0.001) with partner support. HIV prevention interventions aimed at reducing mixed feeding should encourage supportive partner relationships that facilitate disclosure of HIV status. Attention should also be made to the differing pressures faced by women attempting to exclusively breast feed and exclusively formula feed.

Timing and determinants of mother-to-child transmission of HIV in Nigeria.

To characterize the timing and determinants of mother‐to‐child transmission (MTCT) of HIV among mothers receiving single‐dose nevirapine to prevent MTCT in Nigeria.

Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes.