NOHA: A Promising Biomarker for Determining Estrogen Receptor Status Among Patients With Breast Cancer in Resource-Constrained Settings.

PURPOSE: Challenges to breast cancer control in low-and middle-income countries exist because of constrained access to care, including pathology services. Immunohistochemistry (IHC)-based estrogen receptor (ER) analysis is limited-nonexistent because of few and inadequately staffed and equipped pathology laboratories. We have identified Nw-hydroxy-L-Arginine (NOHA) as a blood-based biomarker to distinguish ER status in US patients with breast cancer. Here, we examine NOHA's clinical utility as an ER IHC alternative in Tanzanian patients. MATERIALS AND METHODS: Following informed consent, 70 newly diagnosed, known or suspected patients with breast cancer were enrolled at Kilimanjaro Christian Medical Center; basic, deidentified clinical and sociodemographic data were collected. For each, a needle prick amount of blood was collected on a Noviplex plasma card and stored at -80°C. Plasma cards and unstained tumor pathology slides were shipped regularly to US laboratories for NOHA, histologic and IHC analysis. NOHA and IHC assay operators were blinded to each other's result and patient clinical status. Paired NOHA and IHC results were compared. RESULTS: Slides from 43 participants were available for pathological analysis in the United States. Of those with confirmed malignancy (n = 39), 44%, 51%, 5% were ER-positive, ER-negative, and ER inconclusive, respectively. NOHA levels were available among 33 of 43 of those with pathological data and showed distinct threshold levels correlating 100% to tumor ER IHC and disease categorization where a level below 4 nM, from 4 to 8 nM, and above 8 nM signified ER-negative, ER-positive, and no cancer, respectively. CONCLUSION: The results are consistent with findings from US patients and suggest NOHA's clinical utility as an accessible IHC replacement in determining ER status among low-and middle-income country patients with breast cancer, promising to extend access to cost-efficient, available hormonal agents and improve outcomes.

Iron Depletion, Iron Deficiency, and Iron Deficiency Anaemia Among Children Under 5 Years Old in Kilimanjaro, Northern Tanzania: A Hospital-Based Cross-Sectional Study.

BACKGROUND: Iron depletion results from reduced iron stores, and it is an early stage of disease progression before iron deficiency, which leads to iron deficiency anaemia (IDA). IDA is associated with delayed infant growth and development, diminished cognitive function, poor academic performance, decreased exercise tolerance, and impaired immune function. This study aimed to determine the prevalence of iron depletion and IDA and factors associated with low ferritin levels among children under 5-years-old receiving care at Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania. METHODS: Under-5 children presenting at KCMC were successively enrolled and screened for iron depletion and IDA using complete blood count and serum ferritin levels. The generally accepted World Health Organization cut-off levels for normal haemoglobin (Hb) and ferritin level were used. Iron depletion, iron deficiency, and IDA prevalences were estimated in relation to the combination measures of haemoglobin, mean corpuscular volume, and ferritin levels. Dietary and sociodemographic characteristic of the children were recorded after parents or caretakers provided informed consent. Data analysis was conducted using SPSS version 21.0. RESULTS: A total of 303 children aged 2 to 59 months were enrolled in the study. Anaemia was detected in169 (55.8%) children. Children aged 2 to 12 months had a higher prevalence of anaemia (n=101, 60.1%). The overall prevalences of iron depletion, iron deficiency with no anaemia, and IDA were 2.6% (n=8), 9.6% (n=29), and 28.1% (n=84), respectively. Low ferritin levels were detected in 124 (40.9%) children. Drinking more than 500 ml of cow's milk per day was associated with an increased risk of anaemia (adjusted odds ratio [AOR] 5.6; 95% confidence interval [CI], 2.6 to 12.1) relative to those not drinking cow's milk. Children whose families had meals that included beef more than 3 times per week were less likely to have low ferritin (AOR 0.6; 95% CI, 0.3 to 1.3), though the difference was not significant. CONCLUSION: The IDA prevalence among children in the Kilimanjaro area was high, with more than 50% of infants being anaemic. Drinking cow's milk was associated with an increased risk of IDA. Future community-based research is recommended to elucidate more details about iron deficiency in the general population.

Prevalence of Sickle Cell Disease Among Anaemic Children Attending Mbeya Referral Hospital in Southern Tanzania.

BACKGROUND: Sickle cell disease (SCD) is a common genetic haematological disorder present in most countries in sub-Saharan Africa. In Tanzania, between 50% and 75% of the children born with SCD die before reaching the age of 5 years. The objective of this study was to determine the prevalence of SCD in children under 5 years of age attending Mbeya Referral Hospital between March and April 2014. METHODS: We conducted a hospital-based, cross-sectional, descriptive study in which 50 children under 5 were included at Mbeya Referral Hospital in southern Tanzania. Full blood counts were conducted using SYSMEX KX 21 and SYSMEX XT 2000i haematology analysers. The presence of haemoglobin S was determined using the sodium metabisulfite sickling test on blood samples with haemoglobin levels less than 10 g/dl. RESULTS: Blood samples from 50 infants and children under 5 were tested for sickle cell anaemia. Of these, 9 (18%) participants were found to be sickling test positive, 5 (55.6%) of whom were male and 4 (44.4%) were female. Almost half (n=4, 44.4%) of the SCD-positive children were between 25 and 36 months old, while the rest were between 13 and 24 months (n=2, 22.2%), 37 and 48 months (n=1, 11.1%), and 49 and 60 months (n=2, 22.2%) of age. CONCLUSION: At our facility, among children under 5 with serum haemoglobin levels <10 g/dl, the prevalence of SCD was 18%. This might pose a substantial public health challenge in the region. More and larger studies are needed to help map out the sickle cell burden throughout the country to guide policy and management strategies.

Challenges of Maintaining Good Clinical Laboratory Practices in Low-Resource Settings: A Health Program Evaluation Framework Case Study From East Africa.

OBJECTIVES: Using a clinical research laboratory as a case study, we sought to characterize barriers to maintaining Good Clinical Laboratory Practice (GCLP) services in a developing world setting. METHODS: Using a US Centers for Disease Control and Prevention framework for program evaluation in public health, we performed an evaluation of the Kilimanjaro Christian Medical Centre-Duke University Health Collaboration clinical research laboratory sections of the Kilimanjaro Clinical Research Institute in Moshi, Tanzania. Laboratory records from November 2012 through October 2014 were reviewed for this analysis. RESULTS: During the 2-year period of study, seven instrument malfunctions suspended testing required for open clinical trials. A median (range) of 9 (1-55) days elapsed between instrument malfunction and biomedical engineer service. Sixteen (76.1%) of 21 suppliers of reagents, controls, and consumables were based outside Tanzania. Test throughput among laboratory sections used a median (range) of 0.6% (0.2%-2.7%) of instrument capacity. Five (55.6%) of nine laboratory technologists left their posts over 2 years. CONCLUSIONS: These findings demonstrate that GCLP laboratory service provision in this setting is hampered by delays in biomedical engineer support, delays and extra costs in commodity procurement, low testing throughput, and high personnel turnover.

Establishment of haematological and immunological reference values for healthy Tanzanian children in Kilimanjaro Region.

OBJECTIVE: To determine the normal haematological and immunological reference intervals for healthy Tanzanian children. METHODS: We analysed data from 655 HIV-seronegative, healthy children from 1 month to 18 years of age from the Kilimanjaro Region of Tanzania for this cross-sectional study. Median and 95% reference ranges were determined for haematological and immunological parameters and analysed by age cohorts, and by gender for adolescents. RESULTS: Median haemoglobin (Hb) and haematocrit (Hct) for all age groups were higher than established East African reference intervals. Compared to U.S. intervals, reference ranges encompassed lower values for Hb, Hct, mean corpuscular volume, and platelets. Applying the U.S. National Institute of Health Division of AIDS (DAIDS) adverse event grading criteria commonly used in clinical trials to the reference range participants, 128 (21%) of 619 children would be classified as having an adverse event related to Hb level. CD4-positive T-lymphocyte absolute counts declined significantly with increasing age (P < 0.0001). For those aged under five years, CD4-positive T-lymphocyte percentages are lower than established developed country medians. CONCLUSIONS: Country-specific reference ranges are needed for defining normal laboratory parameters among children in Africa. Knowledge of appropriate reference intervals is critical not only for providing optimal clinical care, but also for enrolling children in medical research. Knowledge of normal CD4-positive T-lymphocyte parameters in this population is especially important for guiding the practice of HIV medicine in Tanzania.