Performance of HRP-2 based rapid diagnostic test for malaria and its variation with age in an area of intense malaria transmission in southern tanzania

BACKGROUND: The use of malaria rapid diagnostic tests (RDTs) has been widely advocated to improve Plasmodium falciparum diagnosis, especially in settings where quality microscopy is not available. RDTs based on the detection of histidine-rich protein 2 (HRP-2) can remain positive for several weeks after an infection is cured, due to the persistence of HRP-2 antigens. As a result, test specificity may vary between age groups with different prevalence of P. falciparum infection. METHODS: A community-based cross-sectional survey, carried out in southern Tanzania in July and August 2004, evaluated the performance of the Paracheck Pf in comparison with microscopy (number of P. falciparum parasites/200 leucocytes). A sample of 598 individuals living in an area of intense malaria transmission had demographic data collected before an RDT was performed. HRP-2 test sensitivity, specificity, positive and negative predictive values were calculated and compared between distinct age groups, using microscopy as "gold standard". RESULTS: The overall malaria prevalence was 34.3% according to microscopy and 57.2% according to the HRP-2 test. The HRP-2 test had a sensitivity of 96.1%, a specificity of 63.1%, a positive predictive value of 57.6% and a negative predictive value of 96.9%. The test sensitivity was higher (ranging from 98% to 100%) amongst people less than 25 years of age, but decreased to 81.3% in older adults. The HRP-2 test specificity varied between age groups, ranging from 25% among children of five to nine years of age, to 73% among adults aged 25 or more. The test positive predictive value increased with malaria prevalence, while the negative predictive value was consistently high across age groups. CONCLUSIONS: These results suggest that the performance of HRP-2 tests in areas of intense malaria transmission varies by age and the prevalence of P. falciparum infection. The particularly low specificity among children will lead to the over-estimation of malaria infection prevalence in this group

Measuring newborn foot length to identify small babies in need of extra care: a cross sectional hospital based study with community follow-up in Tanzania

BACKGROUND\ud \ud Neonatal mortality because of low birth weight or prematurity remains high in many developing country settings. This research aimed to estimate the sensitivity and specificity, and the positive and negative predictive values of newborn foot length to identify babies who are low birth weight or premature and in need of extra care in a rural African setting.\ud \ud METHODS\ud \ud A cross-sectional study of newborn babies in hospital, with community follow-up on the fifth day of life, was carried out between 13 July and 16 October 2009 in southern Tanzania. Foot length, birth weight and gestational age were estimated on the first day and foot length remeasured on the fifth day of life.\ud \ud RESULTS\ud \ud In hospital 529 babies were recruited and measured within 24 hours of birth, 183 of whom were also followed-up at home on the fifth day. Day one foot length <7 cm at birth was 75% sensitive (95%CI 36-100) and 99% specific (95%CI 97-99) to identify very small babies (birth weight <1500 grams); foot length <8 cm had sensitivity and specificity of 87% (95%CI 79-94) and 60% (95%CI 55-64) to identify those with low birth weight (<2500 grams), and 93% (95%CI 82-99) and 58% (95%CI 53-62) to identify those born premature (<37 weeks). Mean foot length on the first day was 7.8 cm (standard deviation 0.47); the mean difference between first and fifth day foot lengths was 0.1 cm (standard deviation 0.3): foot length measured on or before the fifth day of life identified more than three-quarters of babies who were born low birth weight.\ud \ud CONCLUSION\ud \ud Measurement of newborn foot length for home births in resource poor settings has the potential to be used by birth attendants, community volunteers or parents as a screening tool to identify low birth weight or premature newborns in order that they can receive targeted interventions for improved survival

How Mistimed and Unwanted Pregnancies Affect Timing of Antenatal Care Initiation in three Districts in Tanzania

Early antenatal care (ANC) initiation is a doorway to early detection and management of potential complications associated with pregnancy. Although the literature reports various factors associated with ANC initiation such as parity and age, pregnancy intentions is yet to be recognized as a possible predictor of timing of ANC initiation. Data originate from a cross-sectional household survey on health behaviour and service utilization patterns. The survey was conducted in 2011 in Rufiji, Kilombero and Ulanga districts in Tanzania on 910 women of reproductive age who had given birth in the past two years. ANC initiation was considered to be early only if it occurred in the first trimester of pregnancy gestation. A recently completed pregnancy was defined as mistimed if a woman wanted it later, and if she did not want it at all the pregnancy was termed as unwanted. Chisquare was used to test for associations and multinomial logistic regression was conducted to examine how mistimed and unwanted pregnancies affect timing of ANC initiation. Although 49.3% of the women intended to become pregnant, 50.7% (34.9% mistimed and 15.8% unwanted) became pregnant unintentionally. While ANC initiation in the 1st trimester was 18.5%, so was 71.7% and 9.9% in the 2nd and 3rd trimesters respectively. Multivariate analysis revealed that ANC initiation in the 2nd trimester was 1.68 (95% CI 1.10‒2.58) and 2.00 (95% CI 1.05‒3.82) times more likely for mistimed and unwanted pregnancies respectively compared to intended pregnancies. These estimates rose to 2.81 (95% CI 1.41‒5.59) and 4.10 (95% CI 1.68‒10.00) respectively in the 3rd trimester. We controlled for gravidity, age, education, household wealth, marital status, religion, district of residence and travel time to a health facility. Late ANC initiation is a significant maternal and child health consequence of mistimed and unwanted pregnancies in Tanzania. Women should be empowered to delay or avoid pregnancies whenever they need to do so. Appropriate counseling to women, especially those who happen to conceive unintentionally is needed to minimize the possibility of delaying ANC initiation.\u

Duration of Protection against Malaria and Anaemia Provided by Intermittent Preventive Treatment in Infants in Navrongo, Ghana

BACKGROUND: Intermittent preventive treatment for malaria in Infants (IPTi) has been shown to give effective and safe protection against malaria. It has been suggested that IPTi might have long-lasting beneficial effects but, in most settings, the protection provided by IPTi appears to be short-lived. Knowledge of the duration of protection given by IPTi would help interpret the results of existing trials and suggest optimal delivery schedules for IPTi. This study investigated how the protective efficacy of IPTi against malaria and anaemia changes over time. METHODS AND FINDINGS: A secondary analysis of data from a cluster-randomised, placebo-controlled trial of IPTi using sulfadoxine-pyrimethamine (SP) in Ghana was conducted. In this trial IPTi was given to 2485 infants at 3, 4, 9 and 12 months of age; children remained in follow-up until two years of age. Poisson regression with a random effect to adjust for the cluster-randomised design was used to determine protective efficacy of IPTi against clinical malaria and anaemia in defined time strata following administration of IPTi. Analysis of first-or-only clinical malaria episode following the individual IPTi doses showed that some protection against malaria lasted between 4 to 6 weeks. A similar pattern was seen when the incidence of all malaria episodes up to 2 years of age was analysed in relation to the most recent IPT, by pooling the incidence of malaria after the individual IPTi doses. Protective efficacy within four weeks of IPTi was 75.2% (95% CI: 66-82) against malaria, 78.9% (95% CI: 69-86) against high parasite density malaria, and 93.8% (95% CI: 73-99) against anaemia. Protection against these outcomes was short-lived, with evidence of any effect lasting for only 6, 6 and 4 weeks respectively. Protection in children who were parasitaemic when receiving IPTi appeared to be of shorter duration than in uninfected children. There was no evidence of any benefit of IPTi after the immediate period following the IPTi doses. CONCLUSIONS: Intermittent preventive treatment provides considerable protection against malaria and anaemia for short periods, even in an area of intense seasonal transmission. Due to the relatively short duration of protection provided by each dose of IPTi, this treatment will be of most benefit when delivered at the time of peak malaria incidence

Poor newborn care practices - a population based survey in eastern Uganda

BACKGROUND: Four million neonatal deaths are estimated to occur each year and almost all in low income countries, especially among the poorest. There is a paucity of data on newborn health from sub-Saharan Africa and few studies have assessed inequity in uptake of newborn care practices. We assessed socioeconomic differences in use of newborn care practices in order to inform policy and programming in Uganda. METHODS: All mothers with infants aged 1-4 months (n = 414) in a Demographic Surveillance Site were interviewed. Households were stratified into quintiles of socioeconomic status (SES). Three composite outcomes (good neonatal feeding, good cord care, and optimal thermal care) were created by combining related individual practices from a list of twelve antenatal/essential newborn care practices. Multiple logistic regression analysis was used to identify determinants of each dichotomised composite outcome. RESULTS: There were low levels of coverage of newborn care practices among both the poorest and the least poor. SES and place of birth were not associated with any of the composite newborn care practices. Of newborns, 46% had a facility delivery and only 38% were judged to have had good cord care, 42% optimal thermal care, and 57% were considered to have had adequate neonatal feeding. Mothers were putting powder on the cord; using a bottle to feed the baby; and mixing/replacing breast milk with various substitutes. Multiparous mothers were less likely to have safe cord practices (OR 0.5, CI 0.3 - 0.9) as were mothers whose labour began at night (OR 0.6, CI 0.4 - 0.9). CONCLUSION: Newborn care practices in this setting are low and do not differ much by socioeconomic group. Despite being established policy, most neonatal interventions are not reaching newborns, suggesting a "policy-to-practice gap". To improve newborn survival, newborn care should be integrated into the current maternal and child interventions, and should be implemented at both community and health facility level as part of a universal coverage strategy

Assessing agreement between malaria slide density readings

BACKGROUND: Several criteria have been used to assess agreement between replicate slide readings of malaria parasite density. Such criteria may be based on percent difference, or absolute difference, or a combination. Neither the rationale for choosing between these types of criteria, nor that for choosing the magnitude of difference which defines acceptable agreement, are clear. The current paper seeks a procedure which avoids the disadvantages of these current options and whose parameter values are more clearly justified. METHODS AND RESULTS: Variation of parasite density within a slide is expected, even when it has been prepared from a homogeneous sample. This places lower limits on sensitivity and observer agreement, quantified by the Poisson distribution. This means that, if a criterion of fixed percent difference criterion is used for satisfactory agreement, the number of discrepant readings is over-estimated at low parasite densities. With a criterion of fixed absolute difference, the same happens at high parasite densities. For an ideal slide, following the Poisson distribution, a criterion based on a constant difference in square root counts would apply for all densities. This can be back-transformed to a difference in absolute counts, which, as expected, gives a wider range of acceptable agreement at higher average densities. In an example dataset from Tanzania, observed differences in square root counts correspond to a 95% limits of agreement of -2,800 and +2,500 parasites/microl at average density of 2,000 parasites/microl, and -6,200 and +5,700 parasites/microl at 10,000 parasites/microl. However, there were more outliers beyond those ranges at higher densities, meaning that actual coverage of these ranges was not a constant 95%, but decreased with density. In a second study, a trial of microscopist training, the corresponding ranges of agreement are wider and asymmetrical: -8,600 to +5,200/microl, and -19,200 to +11,700/microl, respectively. By comparison, the optimal limits of agreement, corresponding to Poisson variation, are +/- 780 and +/- 1,800 parasites/microl, respectively. The focus of this approach on the volume of blood read leads to other conclusions. For example, no matter how large a volume of blood is read, some densities are too low to be reliably detected, which in turn means that disagreements on slide positivity may simply result from within-slide variation, rather than reading errors. CONCLUSIONS: The proposed method defines limits of acceptable agreement in a way which allows for the natural increase in variability with parasite density. This includes defining the levels of between-reader variability, which are consistent with random variation: disagreements within these limits should not trigger additional readings. This approach merits investigation in other settings, in order to determine both the extent of its applicability, and appropriate numerical values for limits of agreement

Survival of neonates in rural Southern Tanzania: does place of delivery or continuum of care matter?

\ud The concept of continuum of care has recently been highlighted as a core principle of maternal, newborn and child health initiatives, and as a means to save lives. However, evidence has consistently revealed that access to care during and post delivery (intra and postpartum) remains a challenge in the continuum of care framework. In places where skilled delivery assistance is exclusively available in health facilities, access to health facilities is critical to the survival of the mother and her newborn. However, little is known about the association of place of delivery and survival of neonates. This paper uses longitudinal data generated in a Health and Demographic Surveillance System in rural Southern Tanzania to assess associations of neonatal mortality and place of delivery. Three cohorts of singleton births (born 2005, 2006 and 2007) were each followed up from birth to 28 days. Place of birth was classified as either "health facility" or "community". Neonatal mortality rates were produced for each year and by place of birth. Poisson regression was used to estimate crude relative risks of neonatal death by place of birth. Adjusted ratios were derived by controlling for maternal age, birth order, maternal schooling, sex of the child and wealth status of the maternal household. Neonatal mortality for health facility singleton deliveries in 2005 was 32.3 per 1000 live births while for those born in the community it was 29.7 per 1000 live births. In 2006, neonatal mortality rates were 28.9 and 26.9 per 1,000 live births for deliveries in health facilities and in the community respectively. In 2007 neonatal mortality rates were 33.2 and 27.0 per 1,000 live births for those born in health facilities and in the community respectively. Neonates born in a health facility had similar chances of dying as those born in the community in all the three years of study. Adjusted relative risks (ARR) for neonatal death born in a health facility in 2005, 2006 and 2007 were 0.99 (95% CI: 0.58 - 1.70), 0.98 (95% CI: 0.62 - 1.54) and 1.18 (95% CI: 0.76 - 1.85) respectively. We found no evidence to suggest that delivery in health facilities was associated with better survival chances of the neonates.\u

Reduction in the proportion of fevers associated with Plasmodium falciparum parasitaemia in Africa: a systematic review

BACKGROUND: Malaria is almost invariably ranked as the leading cause of morbidity and mortality in Africa. There is growing evidence of a decline in malaria transmission, morbidity and mortality over the last decades, especially so in East Africa. However, there is still doubt whether this decline is reflected in a reduction of the proportion of malaria among fevers. The objective of this systematic review was to estimate the change in the Proportion of Fevers associated with Plasmodium falciparum parasitaemia (PFPf) over the past 20 years in sub-Saharan Africa. METHODS: Search strategy. In December 2009, publications from the National Library of Medicine database were searched using the combination of 16 MeSH terms.Selection criteria. Inclusion criteria: studies 1) conducted in sub-Saharan Africa, 2) patients presenting with a syndrome of 'presumptive malaria', 3) numerators (number of parasitologically confirmed cases) and denominators (total number of presumptive malaria cases) available, 4) good quality microscopy.Data collection and analysis. The following variables were extracted: parasite presence/absence, total number of patients, age group, year, season, country and setting, clinical inclusion criteria. To assess the dynamic of PFPf over time, the median PFPf was compared between studies published in the years ≤2000 and &gt; 2000. RESULTS: 39 studies conducted between 1986 and 2007 in 16 different African countries were included in the final analysis. When comparing data up to year 2000 (24 studies) with those afterwards (15 studies), there was a clear reduction in the median PFPf from 44% (IQR 31-58%; range 7-81%) to 22% (IQR 13-33%; range 2-77%). This dramatic decline is likely to reflect a true change since stratified analyses including explanatory variables were performed and median PFPfs were always lower after 2000 compared to before. CONCLUSIONS: There was a considerable reduction of the proportion of malaria among fevers over time in Africa. This decline provides evidence for the policy change from presumptive anti-malarial treatment of all children with fever to laboratory diagnosis and treatment upon result. This should insure appropriate care of non-malaria fevers and rationale use of anti-malarials

Effect of Supplementation with Zinc and Other Micronutrients on Malaria in Tanzanian Children: A Randomised Trial

Hans Verhoef and colleagues report findings from a randomized trial conducted among Tanzanian children at high risk for malaria. Children in the trial received either daily oral supplementation with either zinc alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. The investigators did not find evidence from this study that zinc or multi-nutrients protected against malaria episodes

Serum after Autologous Transplantation Stimulates Proliferation and Expansion of Human Hematopoietic Progenitor Cells

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34+, CD133+, CD45−) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool