Hepatitis A Antibody Seroprevalence in a Selected Kenyan Pediatric Population

The incidence of infection by Hepatitis A virus shows regional variation being highest in developing countries. Determination of age specific Hepatitis A virus (HAV) seroprevalence and the associated risk factors would help better plan for national preventive strategies including vaccination. We carried out a cross-sectional study on 300 children from Nairobi city, Kenya during the years 2003-2004. The age range of the children was 2 - 14 years and were from low and high socioeconomic status (SES) families. The indicators of SES included employment status, residence, number of children per patient’s household, parents’ level of education and source of drinking water. SES was encoded and analysed using Statistical Program for Social Sciences (SSPS) version 16.0. Seroprevalence increased significantly with advancing age. Seropositivity of HAV antibodies was significantly higher among children of low SES, 77.6% by the age of 14 years compared to children of high SES, 38.9% by the same age. Crowded household and parental education were significantly associated with high seropositivity and seronegativity respectively. There is significant rate of seronegativity amongst the studied population especially those from richer backgrounds making them more susceptible to severe infection in future with concomitant complications. We propose that revision of national vaccination program should be considered to include Hepatitis A vaccination

Saleability of Anti-malarials in Private Drug Shops in Muheza, Tanzania: A Baseline study in an era of assumed Artemisinin Ccombination Therapy (ACT).

Artemether-lumefantrine (ALu) replaced sulphadoxine-pymimethamine (SP) as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT) is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant women depend on SP for Intermittent Preventive Treatment (IPTp) during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform a baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. All drug shops selling prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. All surveyed drug shops illicitly sold SP and quinine (QN), and legally amodiaquine (AQ). Calculated monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local brands of SP accounted for 74% of sales volume, compared to AQ (13%), QN (11%) and ACT (2%). In community practice, the saleability of ACT was negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated in the national anti-malarial policy. It is a major reason for concern that such drug-pressure in the community equals de facto intermittent presumptive treatment. In an area where SP drug resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp strategy. Further studies are recommended to find out barriers for ACT utilization and preference for self-medication and to train private drug dispensers

Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study

Visceral leishmaniasis (VL) is a parasitic disease transmitted through the bite of sandflies. The WHO estimates 500,000 new cases of VL each year, with more than 90% of cases occurring in Southeast Asia, East Africa, and South America. If left untreated, VL can be fatal. We had previously conducted a large multi-center study in Sudan, East Africa, to assess the efficacy of paromomycin (PM) alone or in combination with sodium stibogluconate. Clinical studies in India have shown that 15 mg/kg/day PM for 21 days was an effective cure. However, the same treatment regimen was not efficacious in two study sites in Sudan. Here, our aim was to assess two high-dose regimens of PM in Sudan: 15 mg/kg/day for 28 days and 20 mg/kg/day for 21 days. The results suggest that, at these total doses, PM is more efficacious than when given daily at 15 mg/kg for 21 days, and that high doses are required to treat VL in Sudan. Efficacy of 20 mg/kg/day PM for 21 days is currently being evaluated in a prospective, comparative phase III trial in East Africa

Safety and Efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Treatment options for Visceral Leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa.</p> <p>Methods/Design</p> <p>A phase II randomized, parallel arm, open-labelled trial is being conducted to assess the efficacy of each of the three regimens: liposomal amphotericin B with SSG, Liposomal amphotericin B with miltefosine and miltefosine alone. The primary endpoint is cure at day 28 with secondary endpoint at day 210 (6 months). Initial cure is a single composite measure based on parasitologic evaluation (bone marrow, spleen or lymph node aspirate) and clinical assessment. Repeated interim analyses have been planned after recruitment of 15 patients in each arm with a maximum sample size of 63 for each. These will follow group-sequential methods (the triangular test) to identify when a regimen is inadequate (<75% efficacy) or adequate (>90% efficacy). We describe a method to ensure consistency of the sequential analysis of day 28 cure with the non-sequential analysis of day 210 cure.</p> <p>Discussion</p> <p>A regimen with adequate efficacy would be a candidate for treatment of VL with reasonable costs. The design allows repeated testing throughout the trial recruitment period while maintaining good statistical properties (Type I & II error rates) and reducing the expected sample sizes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01067443">NCT01067443</a></p

Taking stock: provider prescribing practices in the presence and absence of ACT stock

BACKGROUND: Globally, the monitoring of prompt and effective treatment for malaria with artemisinin combination therapy (ACT) is conducted largely through household surveys. This measure; however, provides no information on case management processes at the health facility level. The aim of this review was to assess evidence from health facility surveys on malaria prescribing practices using ACT, in the presence and absence of ACT stock, at time and place where treatment was sought. METHODS: A systematic search of published literature was conducted. Findings were collated and data extracted on proportion of patients prescribed ACT and alternative anti-malarials in the presence and absence of ACT stock. RESULTS: Of the 14 studies identified in which ACT prescription for uncomplicated malaria in the public sector was evaluated, just six, from three countries (Kenya, Uganda and Zambia), reported this in the context of ACT stock. Comparing facilities with ACT stock to facilities without stock (i) ACT prescribing was significantly higher in all six studies, increasing by a range of 21.3% in children < 5 yrs weighing ≥ 5 kg (p < 0.001; Kenya 2006) to 51.7% in children ≥ 10 kg (p < 0.001; Zambia 2006); (ii) SP prescribing decreased significantly in five studies, by a range of 14.4% (p < 0.001; Kenya 2006), to 46.3% (p < 0.001; Zambia 2006); (iii) Where quinine was a reported alternative, prescriptions decreased in five of the six studies by 0.1% (p = 1.0, Kenya 2010) to 10.2% (p < 0.001; Zambia 2006). At facilities with no ACT stock on the survey day, the proportion of febrile patients prescribed ACT was < 10% in five of the nine target groups included in the six studies, with the proportion prescribed ACT ranging from 0 to 28.4% (Uganda 2007). CONCLUSIONS: Prescriber practices vary based on ACT availability. Although ACT prescriptions increased and alternative anti-malarials prescriptions decreased in the presence of ACT stock, ACT was prescribed in the absence, and alternative anti-malarials were prescribed in the presence of, ACT. Presence of stock alone does not ensure that treatment guidelines are followed. More health facility surveys, together with qualitative research, are needed to understand the role of ACT stock-outs on provider prescribing behaviours and preferences

Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa

Background: To expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes. Methods: Data from 3 clinical trials were combined in this study, in which Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative polymerase chain reaction (qPCR) before, during, and up to 6 months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at 6 months. Results: The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within 6 months of follow-up at a cutoff of 20 parasites/mL (area under the curve 0.92, specificity 0.91, sensitivity 0.89). Blood parasite loads correlated well with tissue parasite loads (ρ = 0.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a > 80% power to detect a difference in cure rate between treatment regimens if this difference was high (> 50%) and when minimally 30 patients were included per regimen. Conclusions: Blood Leishmania parasite load determined by qPCR is a promising early biomarker to predict relapse in VL patients. Once optimized, it might be useful in dose finding studies of new chemical entities.This work was supported by the European Union Seventh Framework Programme Africoleish (grant number 305178); the World Health Organization—Special Programme for Research and Training in Tropical Diseases (WHO-TDR); the French Development Agency, France (grant number CZZ2062); UK aid, UK; the Federal Ministry of Education and Research through KfW, Germany; the Medicor Foundation, Liechtenstein; Médecins Sans Frontières, International; the Swiss Agency for Development and Cooperation (SDC), Switzerland (grant number 81017718); the Dutch Ministry of Foreign Affairs (DGIS), the Netherlands (grant number PDP15CH21); the French Ministry for Europe and Foreign Affairs (MEAE), France; The Rockefeller Foundation, USA; BBVA Foundation, Spain; the European Union—AfriKADIA project of the Second European and Developing Countries Clinical Trials Partnership Programme (EDCTP2) (grant number RIA2016S1635); and ZonMw/Dutch Research Council (NWO) Veni grant (project number 91617140 to T. P. C. D.).S

The effect of maternal anthropometric characteristics and social factors on gestational age and birth weight in Sudanese newborn infants

<p>Abstract</p> <p>Background</p> <p>In Africa low birth weight (LBW) (<2500 g), is the strongest determinant of infant morbidity and mortality. The aim of this study was to quantify the effect of maternal anthropometry, education and socio-economic status on gestational age and birth weight.</p> <p>Methods</p> <p>In 1000 Sudanese mothers with singleton births, anthropometric measurements (weight, height, mid-arm circumference) and newborn birth weight were taken within 24 hours of delivery. Furthermore, maternal education and socio-economic status were recorded. The effect of these maternal variables on gestational age and birth weight was investigated by receiver operating characteristic (ROC) curves and by multivariate logistic regression analysis.</p> <p>Results</p> <p>Although maternal height was significantly correlated (p = 0.002) with gestational age, we did not find maternal characteristics of value in determining the risk for preterm birth. Birth order was the strongest determinant of birth weight compared to other maternal characteristics. The LBW rate of first born babies of 12.2% was nearly twice that of infants of multiparous mothers. Maternal age and all maternal anthropometric measurements were positively correlated (p < 0.001) with birth weight. A maternal height of <156 cm, a maternal weight of <66 kg, a maternal mid arm circumference of <27 cm and years of education of ≤ 8 years were found to increase the relative risk of LBW but this was statistically significant only in the case of maternal height. Maternal age and BMI had no statistically significant effect on determining the risk for LBW. The social class did not affect the birth weight, while the number of years of education was positively correlated with birth weight (p = 0.01). The LBW rate decreased from 9.2% for ≤ 8 years of education to 6.0% for >12 years of education.</p> <p>Conclusion</p> <p>Birth order and maternal height were found to be the most important maternal parameters which influences birth weight and the risk for LBW. The duration of maternal education and not social class was found to significantly affect the risk for LBW.</p

Implementation of a structured paediatric admission record for district hospitals in Kenya – results of a pilot study

BACKGROUND: The structured admission form is an apparently simple measure to improve data quality. Poor motivation, lack of supervision, lack of resources and other factors are conceivably major barriers to their successful use in a Kenyan public hospital setting. Here we have examined the feasibility and acceptability of a structured paediatric admission record (PAR) for district hospitals as a means of improving documentation of illness. METHODS: The PAR was primarily based on symptoms and signs included in the Integrated Management of Childhood Illness (IMCI) diagnostic algorithms. It was introduced with a three-hour training session, repeated subsequently for those absent, aiming for complete coverage of admitting clinical staff. Data from consecutive records before (n = 163) and from a 60% random sample of dates after intervention (n = 705) were then collected to evaluate record quality. The post-intervention period was further divided into four 2-month blocks by open, feedback meetings for hospital staff on the uptake and completeness of the PAR. RESULTS: The frequency of use of the PAR increased from 50% in the first 2 months to 84% in the final 2 months, although there was significant variation in use among clinicians. The quality of documentation also improved considerably over time. For example documentation of skin turgor in cases of diarrhoea improved from 2% pre-intervention to 83% in the final 2 months of observation. Even in the area of preventive care documentation of immunization status improved from 1% of children before intervention to 21% in the final 2 months. CONCLUSION: The PAR was well accepted by most clinicians and greatly improved documentation of features recommended by IMCI for identifying and classifying severity of common diseases. The PAR could provide a useful platform for implementing standard referral care treatment guidelines