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Background: Pregnant HIV-infected women were screened for the development of HIV-1 drug resistance after implementation of a triple-antiretroviral transmission prophylaxis as recommended by the WHO in 2006. The study offered the opportunity to compare amplicon-based 454 ultra-deep sequencing (UDS) and allele-specific real-time PCR (ASPCR) for the detection of drug-resistant minor variants in the HIV-1 reverse transcriptase (RT)., Methods: Plasma samples from 34 Tanzanian women were previously analysed by ASPCR for key resistance mutations in the viral RT selected by AZT, 3TC, and NVP (K70R, K103N, Y181C, M184V, T215Y/F). In this study, the RT region of the same samples was investigated by amplicon-based UDS for resistance mutations using the 454 GS FLX System., Results: Drug-resistant HIV-variants were identified in 69% (20/29) of women by UDS and in 45% (13/29) by ASPCR. The absolute number of resistance mutations identified by UDS was twice that identified by ASPCR (45 vs 24). By UDS 14 of 24 ASPCR-detected resistance mutations were identified at the same position. The overall concordance between UDS and ASPCR was 61.0% (25/41). The proportions of variants quantified by UDS were approximately 2-3 times lower than by ASPCR. Amplicon generation from samples with viral loads below 20,000 copies/ml failed more frequently by UDS compared to ASPCR (limit of detection = 650 copies/ml), resulting in missing or insufficient sequence coverage., Conclusions: Both methods can provide useful information about drug-resistant minor HIV-1 variants. ASPCR has a higher sensitivity than UDS, but is restricted to single resistance mutations. In contrast, UDS is limited by its requirement for high viral loads to achieve sufficient sequence coverage, but the sequence information reveals the complete resistance patterns within the genomic region analysed. Improvements to the UDS limit of detection are in progress, and UDS could then facilitate monitoring of drug-resistant minor variants in the HIV-1 quasispecies.

Providing full antiretroviral therapy (ART) to all HIV-positive, pregnant women with treatment indication could significantly reduce overall mother-to-child transmission. However, the effectiveness of referring HIV-positive antenatal care (ANC) clients with a treatment indication to ART services has rarely been assessed to date. We retrospectively followed-up data of a cohort of treatment-eligible ANC clients in Mbeya Region, Tanzania by retracing and merging registries of ANC, Care and Treatment Centers (CTC), and Infant Care. ART initiation and ART duration before delivery served as primary outcome indicators to assess referral effectiveness. We retraced data of 60 ANC clients with treatment indication: 39 (65%) started predelivery ART and 21 (35%) remained untreated during pregnancy. Eight (13.3%) did not initiate ART at all within the observation period. Women starting ART before delivery had significantly lower CD4-cell counts at enrollment than nonstarters (medians: 207.5 vs. 292 cells/µl; p = 0.013). Predelivery ART starters had experienced a significantly shorter duration between staff-declared "ART readiness" and actual ART start (medians: 0 vs. 28 days; p = 0.0004). The median ART duration prior to delivery was 57 days; only eight women (13.3%) accomplished ≥90 days ART intake during pregnancy. Early enrollment in ANC at ≤24 gestational weeks was associated with longer duration of predelivery ART. At maternity wards, 24.3% of treatment-eligible mothers and newborns with retraceable delivery data had received no or inadequate antiretrovirals. Within 6 months postdelivery, women attended on average 3.5 out of 6 requested CTC visits. Concluding, every third treatment-eligible woman in this cohort was not covered through ART before delivery, and predelivery ART duration was mostly suboptimal regarding vertical transmission prevention. HIV-positive women need to be encouraged to approach ANC early in pregnancy, and health services need to address unnecessary time gaps before ART initiation. In addition, inclusive ART services for HIV-positive ANC clients should be seriously discussed.

Background: Schistosomiasis is common in many African regions and poses a risk for travelers and the local population. So far, schistosomiasis in travelers or expatriates returning from the Tanzanian bank of Lake Tanganyika has not been reported., Methods: We report a group of students who sought treatment with signs of acute schistosomiasis after having returned from Lake Tanganyika, Tanzania. Information as to travel and exposure as well as clinical and laboratory data were collected., Results: Schistosomiasis was diagnosed in 8 of 16 students from Berlin, Germany, who had returned from a 2- to 3-month stay of fieldwork in Kigoma District at Lake Tanganyika, Tanzania. All 16 students reported frequent freshwater exposure at the lake. Six patients showed signs of acute schistosomiasis and had fever, and some of them also had cough, weakness, headache, or abdominal pain. Eosinophilia was present in five of the six symptomatic individuals. Notably, two serologically enzyme-linked immunosorbent assay (ELISA)-positive individuals did not report or present with symptoms or abnormal laboratory parameters. Schistosoma mansoni eggs were found in one symptomatic and one asymptomatic individual each. Blood and stool samples from the other eight individuals who were equally exposed to freshwater yielded negative results., Conclusions: This is the first report of an outbreak of acute schistosomiasis imported from the Tanzanian shore of Lake Tanganyika and highlights the risk for travelers and the local population of acquiring the infection in that part of Tanzania. It provides arguments for routine serological screening for schistosomiasis in individuals who had prior freshwater contact in endemic areas, irrespective of symptoms or other laboratory findings., (© 2013 International Society of Travel Medicine.)

Introduction: Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1-4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants., Methods and Materials: A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4-6 and 12., Results: For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4-6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2., Conclusions: AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health.

Background: WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis., Method: 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1-2, 4-6 and 12-16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of <1%., Results: 50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39-64); all women ingested NVP-SD, 86% took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70% displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three women harbored resistant HIV-1 against more than one drug. 49/50 infants, including the seven vertically HIV-infected were breastfed, 3/7 infants exhibited drug-resistant virus., Conclusion: Complex prophylaxis resulted in lower levels of NVP-selected resistance as compared to NVP-SD, but AZT-resistant HIV-1 emerged in a substantial proportion of women. Starting AZT in pregnancy week 14 instead of 28 as recommended by the current WHO-guidelines may further increase the frequency of AZT-resistance mutations. Given its impact on HIV-transmission rate and drug-resistance development, HAART for all HIV-positive pregnant women should be considered.

Background: Zidovudine (AZT) constitutes part of the recommended regimens for prevention and treatment of HIV-1 infection. At the same time, AZT as well as HIV-1 infection itself may induce mitochondrial damage. In this study, we analyzed the impact of prenatal AZT-exposure on mitochondrial alterations in HIV-infected women and their infants., Methods: Mitochondrial DNA (mtDNA) levels in placentas of HIV-1 infected Tanzanian women with and without prenatal AZT exposure, and in the umbilical cords of their AZT-exposed/unexposed infants were quantified using real-time PCR. Furthermore, we checked for the most common mitochondrial deletion in humans, the 4977 base pair deletion (dmtDNA4977) as a marker for mitochondrial stress., Results: 83 women fulfilled the inclusion criteria. 30 women had been treated with AZT (median duration 56 days; IQR 43-70 days) while 53 women had not taken AZT during pregnancy. Baseline maternal characteristics in the two groups were similar. The median mtDNA levels in placentas and umbilical cords of women (311 copies/cell) and infants (190 copies/cell) exposed to AZT were significantly higher than in AZT-unexposed women (187 copies/cell; p = 0.021) and infants (127 copies/cell; p = 0.037). The dmtDNA4977 was found in placentas of one woman of each group and in 3 umbilical cords of AZT-unexposed infants but not in umbilical cords of AZT-exposed infants., Conclusions: Antenatal AZT intake did not increase the risk for the common mitochondrial deletion dmtDNA4977. Our data suggests that AZT exposure elevates mtDNA levels in placentas and umbilical cords possibly by positively influencing the course of maternal HIV-1 infection.

Background: Since 2008, Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend combination regimen for mother and infant starting in gestational week 28. Combination prophylaxis is assumed to be more effective and less prone to resistance formation compared to single-drug interventions, but the required continuous collection and intake of drugs might pose a challenge on adherence especially in peripheral resource-limited settings. This study aimed at analyzing adherence to combination prophylaxis under field conditions in a rural health facility in Kyela, Tanzania., Methods and Findings: A cohort of 122 pregnant women willing to start combination prophylaxis in Kyela District Hospital was enrolled in an observational study. Risk factors for decline of prophylaxis were determined, and adherence levels before, during and after delivery were calculated. In multivariate analysis, identified risk factors for declining pre-delivery prophylaxis included maternal age below 24 years, no income-generating activity, and enrolment before 24.5 gestational weeks, with odds ratios of 5.8 (P = 0.002), 4.4 (P = 0.015) and 7.8 (P = 0.001), respectively. Women who stated to have disclosed their HIV status were significantly more adherent in the pre-delivery period than women who did not (P = 0.004). In the intra- and postpartum period, rather low drug adherence rates during hospitalization indicated unsatisfactory staff performance. Only ten mother-child pairs were at least 80% adherent during all intervention phases; one single mother-child pair met a 95% adherence threshold., Conclusions: Achieving adherence to combination prophylaxis has shown to be challenging in this rural study setting. Our findings underline the need for additional supervision for PMTCT staff as well as for clients, especially by encouraging them to seek social support through status disclosure. Prophylaxis uptake might be improved by preponing drug intake to an earlier gestational age. Limited structural conditions of a healthcare setting should be taken into serious account when implementing PMTCT combination prophylaxis.

Partner involvement is considered to increase the effectiveness of female-oriented services for sexual and reproductive health (SRH), like those for antenatal care (ANC) or the prevention of mother-to-child transmission of HIV (PMTCT). However, male participation rates remain mostly low, and previous research has identified restrictive provider attitudes among barriers for partner participation in such services. Individual perspectives and experiences of healthcare providers are assumed to significantly influence the quality of delivered services. This study aimed at exploring providers' attitudes regarding partner involvement in ANC/PMTCT and other SRH services. A hundred interviews based on a semi-structured questionnaire were conducted among healthcare providers employed in an ANC-based PMTCT program in Mbeya Region, Tanzania. Interviewees expressed overall approval of male partner integration into the services, but this approval decreased when specifying for different service types, especially in those related to perinatal examinations or labor and delivery. Divergence between general attitudes and self-reported individual behavior was observed, querying the reliability of expressed attitudes. Among providers having at least one child, personally experienced partner attendance and approval of partner involvement were significantly associated for most service types. Although general views on partner involvement in SRH services seem to be mostly supportive, there is a need for health services to strengthen providers' positions toward male involvement, for example by communicating clear policies and job guidelines, and by encouraging partner service attendance among providers themselves.

Throughout all stages of programmes for the prevention of mother-to-child-transmission of HIV (PMTCT), high dropout rates are common. Increased male involvement and couples' joint HIV counselling/testing during antenatal care (ANC) seem crucial for improving PMTCT outcomes. Our study assessed male attitudes regarding partner involvement into ANC/PMTCT services in Mbeya Region, Tanzania, conducting 124 individual interviews and six focus group discussions. Almost all respondents generally supported PMTCT interventions. Mentioned barriers to ANC/PMTCT attendance included lacking information/knowledge, no time, neglected importance, the services representing a female responsibility, or fear of HIV-test results. Only few perceived couple HIV counselling/testing as disadvantageous. Among fathers who had refused previous ANC/PMTCT attendance, most had done so even though they were not perceiving a disadvantage about couple counselling/testing. The contradiction between men's beneficial attitudes towards their involvement and low participation rates suggests that external barriers play a large role in this decision-making process and that partner's needs should be more specifically addressed in ANC/PMTCT services.

Objective: Prevention-of-mother-to-child transmission (PMTCT) interventions based on single-dose nevirapine (NVP) are widely implemented in Africa, but strategies differ regarding how and when to administer the drug to women and infants. The aim of this study was to analyze the outcome of different strategies with regard to NVP intake in pregnant women and their infants in Tanzania and Uganda., Methods: In an observational study carried out between March 2002 and December 2004, we compared a directly observed NVP administration strategy in Tanzania (supervised NVP intake for women and infants at a health unit) and a semi-observed administration strategy (self-administered NVP for women at home and supervised intake for infants at a health unit) in Uganda., Results: The proportions of HIV-positive women accepting receipt of NVP from the health units were similar in the 2 countries (42.4% in Tanzania vs 45.6% in Uganda; P = .06). NVP intake in infants was significantly higher in Tanzania than in Uganda (43.7% vs 24.1%; P > .001). In a multivariate analysis, maternal age above 25 years, secondary education, Catholic faith, and having undergone PMTCT counseling at a hospital were independently associated with infant NVP intake., Conclusion: In our settings, the directly observed administration strategy resulted in a higher NVP intake in infants. The semi-observed strategy, which implies that, after home delivery, the infant has to be presented to a health unit for NVP administration, was less successful.

Awareness and knowledge about HIV mother-to-child transmission (MTCT) and preventive measures in different population groups and health personnel were analysed in future intervention areas in western Uganda and southwestern Tanzania. In Uganda, a total of 751 persons (440 clients of antenatal and outpatient clinics, 43 health workers, 239 villagers, 29 traditional birth attendants) and in Tanzania, 574 persons (410 clients, 49 health workers, 93 villagers, 18 traditional birth attendants) were interviewed. When given options, knowledge on transmission during pregnancy and delivery in women was 93% and 67% in Uganda and Tanzania respectively, and 86% and 78% for transmission during breastfeeding. In Uganda 59% of male interviewees did not believe that HIV is transmitted during breastfeeding. Expressed acceptance of HIV testing was above 90% in men and women in both countries, but only 10% of the clients in Uganda and 14% in Tanzania had been tested for HIV infection. Health workers' knowledge regarding MTCT was acceptable, while traditional birth attendants' knowledge on both MTCT and preventive measures was extremely poor. Recom endations on infant feeding were not compatible with WHO recommendations for HIV-infected women. If prevention of MTCT (PMTCT) interventions are to be accepted by the population and promoted by health personnel, thorough orientation and training are mandatory.