Early infant diagnosis of HIV in three regions in Tanzania; successes and challenges.

BACKGROUND: By the end of 2009 an estimated 2.5 million children worldwide were living with HIV-1, mostly as a consequence of vertical transmission, and more than 90% of these children live in sub-Saharan Africa. In 2008 the World Health Organization (WHO), recommended early initiation of Highly Active Antiretroviral Therapy (HAART) to all HIV infected infants diagnosed within the first year of life, and since 2010, within the first two years of life, irrespective of CD4 count or WHO clinical stage. The study aims were to describe implementation of EID programs in three Tanzanian regions with differences in HIV prevalences and logistical set-up with regard to HIV DNA testing. METHODS: Data were obtained by review of the prevention from mother to child transmission of HIV (PMTCT) registers from 2009-2011 at the Reproductive and Child Health Clinics (RCH) and from the databases from the Care and Treatment Clinics (CTC) in all the three regions; Kilimanjaro, Mbeya and Tanga. Statistical tests used were Poisson regression model and rank sum test. RESULTS: During the period of 2009 - 2011 a total of 4,860 exposed infants were registered from the reviewed sites, of whom 4,292 (88.3%) were screened for HIV infection. Overall proportion of tested infants in the three regions increased from 77.2% in 2009 to 97.8% in 2011. A total of 452 (10.5%) were found to be HIV infected (judged by the result of the first test). The prevalence of HIV infection among infants was higher in Mbeya when compared to Kilimanjaro region RR = 1.872 (95%CI = 1.408 - 2.543) p < 0.001. However sample turnaround time was significantly shorter in both Mbeya (2.7 weeks) and Tanga (5.0 weeks) as compared to Kilimanjaro (7.0 weeks), p=<0.001. A substantial of loss to follow-up (LTFU) was evident at all stages of EID services in the period of 2009 to 2011. Among the infants who were receiving treatment, 61% were found to be LFTU during the review period. CONCLUSION: The study showed an increase in testing of HIV exposed infants within the three years, there is large variations of HIV prevalence among the regions. Challenges like; sample turnaround time and LTFU must be overcome before this can translate into the intended goal of early initiation of lifelong lifesaving antiretroviral therapy for the infants.

Orientia tsutsugamushi detected by microbiome diagnostics.

Scrub typhus is caused by the mite-borne bacterium Orientia tsutsugamushi. Imported cases have been suspected in Denmark but no diagnostic method has yet been available to confirm the diagnosis. This is a case report of a 38-year-old male admitted to hospital with high fever, severe malaise and headache after returning from Malaysia. Scrub typhus was suspected and the patient recovered after one week of doxycycline treatment. The pathogen was identified by use of microbiome 16S/18S rRNA next-generation sequencing on ethylenediamine tetraacetic acid (EDTA) blood, which in the future may serve an important role in the investigation of travel-associated infections.

Determination of HIV status of infants born to HIV-infected mothers: a review of the diagnostic methods with special focus on the applicability of p24 antigen testing in developing countries.

In 2009, 2.5 million children under the age of 15 y were living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS); 370,000 were diagnosed with HIV and 260,000 died due to AIDS. More than 90% of the children infected with HIV live in sub-Saharan Africa. Most children infected with HIV contract the infection in utero, during delivery, or via breast milk. This review outlines the current diagnostic methods to determine the HIV status of infants born to HIV-infected mothers. The HIV DNA and RNA polymerase chain reaction (PCR) tests are highly accurate and are recommended as the first-choice diagnostic methods. However, they are expensive and require complex laboratory procedures. Consequently, a search for less costly and complicated methods has led to the testing of p24 antigen analyses as an alternative to the gold-standard PCR tests, with encouraging results. The p24 antigen Perkin Elmer assay currently most often used has a sensitivity of 98.8% and a specificity of 100% (infants 6 weeks of age). Larger-scale studies should be performed in resource-limited settings to confirm these findings.

Evaluation of HIV viral load turnaround time in Moshi, Tanzania.

INTRODUCTION: Viral load measurement is an important gold standard for monitoring anti-retroviral treatment among people living with human immunodeficiency virus. The optimal use of the viral load results for guiding antiretroviral therapy depends on timely availability of the results at the clinic. The objective of the current study was to evaluate the turnaround time and utilization of viral load results in the clinical decision process. METHODOLOGY: This was a retrospective cohort study which involved patients receiving cART from 1 August 2018 to 31 January 2017 at three clinics in Tanzania. Data was extracted from patient files at the clinics and relevant records were kept at the viral load determining laboratory. The data were analysed with the Statistical Package for Social Sciences version 20. RESULTS: 445 subjects had a viral load in test results and 88% had a viral load of > 1,000 copies/mL. The median duration on the current regimen was five years. Median time between the clinics receiving the results and communicating them to the patients was 40 days. Shorter turnaround time was observed for patients with virological failure (p = 0.003). A higher prevalence of virological failure was found in patients monitored at the Kilimanjaro Christian Medical Centre (KCMC) compared to the two primary health clinics (p = 0.04). CONCLUSIONS: The median viral load turnaround time was longer than stipulated by the national Tanzanian guidelines. Interventions that may reduce viral load turn-around-time, including point of care viral load testing, are needed to optimise monitoring of anti-retroviral therapy.

Good performance of an immunoassay based method for nevirapine measurements in human breast milk.

BACKGROUND: Understanding the distribution of antiretro-virals in breastfeeding HIV-positive mothers is essential, both for prevention of mother-to-child HIV transmission and for research on the development of drug resistance. The ARK nevirapine (NVP)-test is an immunoassay method for nevirapine measurements, developed and validated for plasma use. In this study, the ARK NVP-test was evaluated for measurement of nevirapine concentrations in breast milk. High performance liquid chromatography (HPLC) is the method currently used to determine nevirapine in breast milk. This method, however, requires complicated extraction techniques. The ARK method employs an immunoassay technology and requires a small sample volume (40 µL) and no pre-treatment of the samples. METHODS: Commercial enzyme and antibody were used and calibration standards and quality controls were prepared from pooled breast milk from HIV-uninfected women. Clinical samples from HIV-infected women receiving a single-dose of nevirapine were analyzed. RESULTS: Precision and accuracy were evaluated with two concentrations of quality control materials analyzed in three replicates on four different days and was <4%, and between 96.5% and 104.6%, respectively. Clinical samples were analyzed and CVs ranged from 0.0% to 11.1%. The median nevirapine concentration in breast milk 1 week post-partum was 0.29 µg/mL (range 0.11-0.90 µg/mL) in women treated with a single-dose of nevirapine. CONCLUSIONS: The ease of use and small sample volume makes the ARK assay an attractive alternative to HPLC analyses for determinations of nevirapine concentrations in breast milk.

Addressing the fear and consequences of stigmatization - a necessary step towards making HAART accessible to women in Tanzania: a qualitative study.

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) has been available free of charge in Tanga, Tanzania since 2005. However we have found that a high percentage of women referred from prevention of mother-to-child transmission services to the Care and Treatment Clinics (CTC) for HAART never registered at the CTCs. Few studies have focused on the motivating and deterring factors to presenting for HAART particularly in relation to women. This study seeks to remedy this gap in knowledge. METHODOLOGY: A qualitative approach using in-depth interviews and focus group discussions was chosen to understand these issues as perceived and interpreted by HIV infected women themselves. RESULTS: The main deterrent to presenting for treatment appears to be fear of stigmatization including fear of ostracism from the community, divorce and financial distress. Participants indicated that individual counselling and interaction with other people living with HIV encourages women, who are disinclined to present for HAART, to do so, and that placing the entrance to the CTC so as to provide discrete access increases the accessibility of the clinic. CONCLUSION: Combating stigma in the community, although it is essential, will take time. Therefore necessary steps towards encouraging HIV infected women to seek treatment include reducing self-stigma, assisting them to form empowering relationships and to gain financial independence and emphasis by example of the beneficial effect of treatment for themselves and for their children. Furthermore ensuring a discrete location of the CTC can increase its perceived accessibility.

Herpes Simplex virus type 2 seroprevalence and risk factors among adolescents and youth with HIV-1 in Northern, Tanzania.

INTRODUCTION: Herpes Simplex virus type 2 (HSV-2) infection is associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition and transmission. Individuals co-infected with HIV-1 and HSV-2 may have longer lasting, more frequent and severe outbreaks of herpes symptoms. Previous studies have assessed HSV-2 seroprevalence and associated risk factors in adult populations. However, there is limited data on the HSV-2 seroprevalence among adolescents and youth living with HIV-1. The study aimed to determine the HSV-2 seroprevalence and associated risk factors among adolescents and youth living with HIV-1 at referral hospital setting in Northern Tanzania. METHODOLOGY: A cross-sectional survey was conducted between February and July 2017 among HIV-1-infected individuals aged 10-24 years attending the Child -Centred Family Care Clinic at Kilimanjaro Christian Medical Centre. Blood specimens from 180 individuals were collected for ELISA-based detection of HSV-2 antibodies. Associations between risk factors and HSV-2 seroprevalence were analysed by univariate and multivariate logistic regression models. RESULTS: The overall HSV-2 seroprevalence was 18% (32/180). A significant HSV-2 seroprevalence was noted among adolescents and youth, who reported having had sexual intercourse than those who never had sexual intercourse (28.9% vs 13.3%, p = 0.02). Youths aged 20-24 had six folds higher risk of HSV-2 seroprevalence compared to those aged 10-14 years (AOR = 5.97 95% CI 1.31 - 27.19, p = 0.02). CONCLUSIONS: Our study found that HSV-2 seroprevalence increased by age among adolescents and youth living with HIV-1. Age-specific approaches might play an important role in interventions targeting HSV-2 infection.

Retired Nurses Can Improve Retention in Prevention of Mother-to-Child Transmission Programmes.

BACKGROUND: The success of prevention of mother-to-child transmission (PMTCT) programmes depends on retention of mothers throughout the PMTCT cascade. METHODS: In a clinical trial of short-course combination antiretroviral therapy (cART) for PMTCT in Tanzania, senior nurses were employed to reduce the substantial loss-to-follow up (LTFU) rate. RESULTS: Following intervention, the relative risk (RR) of receiving a CD4 count result and antiretroviral therapy was 1.16 (95% confidence interval [CI], 1.05 to 1.27), the RR of delivery at clinic was 2.51 (95% CI, 2.06 to 3.06), the RR for reporting for follow-up at 6 to 8 weeks postpartum was 4.63 (95% CI, 3.41 to 6.27), and the RR for being retained until 9 months postpartum was 28.19 (95% CI, 11.81 to 67.28). No significant impact on transmission was found. CONCLUSION: Significantly higher retention was found after senior nurses were employed. No impact on transmission was found. Relatively low transmission was found in both study arms.

Hepatitis E virus epidemiology among HIV-infected women in an urban area in Tanzania.

OBJECTIVES: This study was performed to determine the seroprevalence and incidence of hepatitis E virus (HEV) infection among HIV-infected women during pregnancy and after delivery in a cohort of 200 Tanzanian women. METHODS: HIV-infected women participating in a study on antiretroviral therapy for the prevention of mother-to-child HIV transmission between 2006 and 2011, were tested retrospectively for anti-HEV immunoglobulin G (IgG) in plasma samples at 9 months post-partum. Anti-HEV IgG-positive patients were tested for anti-HEV IgG and immunoglobulin M (IgM) in samples from enrolment, and seroconverting women were tested for HEV RNA. RESULTS: A total of 16 women were anti-HEV IgG-positive, two of whom had seroconverted between enrolment and 9 months post-partum, with no detection of anti-HEV IgM or HEV RNA, yielding an HEV seroprevalence of 8.0% (confidence interval 5.0-12.6%) and an annual incidence rate of 1.0% (confidence interval 0.2-3.4%). CD4 cell counts were relatively high (median 403×106/l), with no significant difference between women with and without serological signs of HEV. CONCLUSIONS: An annual HEV infection incidence rate of 1% strongly indicates ongoing transmission of HEV in Tanzania and should be kept in mind for pregnant women presenting with signs of acute hepatitis.

Nevirapine, sodium concentration and HIV-1 RNA in breast milk and plasma among HIV-infected women receiving short-course antiretroviral prophylaxis.

INTRODUCTION: Risk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis. OBJECTIVE: To determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine). METHODS: Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant. RESULTS: HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median (interquartile range, IQR) of 1.5 µg/mL (0.75-2.20 µg/mL) and 1.04 µg/mL (0.39-1.71 µg/mL), respectively (P < 0.001). At 1 week postpartum, 93% and 98% of the women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 µg/mL (0.13-0.39 µg/mL) and 0.22 µg/mL (0.13-0.34 µg/mL), respectively. Maternal plasma and breast milk HIV-1 RNA correlated at all visits (R = 0.48, R = 0.7, R = 0.59; all P = 0.01). Subclinical mastitis was detected in 67% of the women at some time during 6 weeks, and in 38% of the breast milk samples. Breast milk samples with subclinical mastitis had significantly higher HIV-1 RNA at 1, 4 and 6 weeks (all P < 0.05). CONCLUSION: After short-course antiretroviral prophylaxis, nevirapine was detectable in most infant cord blood samples and the concentration in maternal plasma and breast milk was high through week 1 accompanied by suppressed HIV-1 RNA in plasma and breast milk.

Referral success among HIV-infected women and HIV-exposed children referred for monitoring and treatment in Tanga, Tanzania.

Long-term retention of patients in the rapidly expanding antiretroviral programs against HIV/AIDS is essential for the success of these programs. Unfortunately, high percentages of patients in need of treatment are lost to follow up in resource-poor settings. From June 2006 to March 2007 269 HIV-infected pregnant women were screened for participation in a Prevention of Mother to Child Transmission (PMTCT) study in Tanga, Tanzania. Ninety-one women were referred to Care and Treatment Center (CTC) for monitoring and antiretroviral therapy regardless of inclusion in the PMTCT study. Both women and HIV-exposed children were traced at CTC from mid-February to mid-March 2008. Follow-up visits for all patients were examined. Only 10% (9/91) of the referred women were still attending CTC by February/March 2008 and 64% (58/91) never attended CTC. Not a single child could be traced at CTC. The largest loss of patients occurs between referral and the first attendance at CTC. Every effort must be made to clarify reasons for loss of patients at this point. Further, measures to improve patient retention must be increased as must initiatives to improve the ability to trace and retain children within the clinics.