Inter-observer variation in the assessment of clinical signs in sick Tanzanian children

We assessed the inter-observer agreement in identification of a range of 24 clinical signs associated with disease presentation in 327 children aged 0·41) although there was only fair agreement (Kappa-score 0·21-0·40) in the detection of neck stiffness and chest indrawing and slight agreement in the detection of dehydration (Kappa-score 0·199). All objective neurological signs were less reliably assessed in infants than in older children. The difficulties surrounding the diagnosis of impaired consciousness in young children should increase vigilance in the diagnosis and management of neurological complications of illnesses in infanc

The incidence of clinical malaria detected by active case detection in children in Ifakara, southern Tanzania

Between July 2000 and June 2001, we used weekly active case detection (ACD) of clinical malaria episodes in 618 children aged <5 years to describe the epidemiology of malaria in Ifakara, southern Tanzania. Plasmodium falciparum-positive blood slides prepared from children with axillary temperature ⩾ 37.5°C were used to define clinical malaria and a rolling cross-sectional survey documented the prevalences of parasitaemia and anaemia. A random subsample of children was visited daily for 1 month at the end of the study to assess the effect of more frequent visits on estimated incidence rates. Only 50 (8%) children had 1 or more episodes of clinical malaria during the year, an overall incidence of 0.275 episodes/100 child-weeks-at-risk, with no age dependence. The maximum parasite prevalence of 25% was reached in children aged 4 years. The incidence of illness was significantly lower in children visited daily than in those visited weekly., suggesting a marked effect of frequent visits on estimated incidence rates. We conclude that the age pattern of malaria detected through ACD is a more robust epidemiological indicator than absolute incidence rate estimates and that, in contrast to the surrounding area, Ifakara town is subject to only moderate perennial malaria transmissio

Point-of-care measurement of blood lactate in children admitted with febrile illness to an African District Hospital.

BACKGROUND: Lactic acidosis is a consistent predictor of mortality owing to severe infectious disease, but its detection in low-income settings is limited to the clinical sign of "deep breathing" because of the lack of accessible technology for its measurement. We evaluated the use of a point-of-care (POC) diagnostic device for blood lactate measurement to assess the severity of illness in children admitted to a district hospital in Tanzania. METHODS: Children between the ages of 2 months and 13 years with a history of fever were enrolled in the study during a period of 1 year. A full clinical history and examination were undertaken, and blood was collected for culture, microscopy, complete blood cell count, and POC measurement of blood lactate and glucose. RESULTS: The study included 3248 children, of whom 164 (5.0%) died; 45 (27.4%) of these had raised levels of blood lactate (>5 mmol/L) but no deep breathing. Compared with mortality in children with lactate levels of ≤ 3 mmol/L, the unadjusted odds of dying were 1.6 (95% confidence interval [CI].8-3.0), 3.4 (95% CI, 1.5-7.5), and 8.9 (95% CI, 4.7-16.8) in children with blood lactate levels of 3.1-5.0, 5.1-8.0, or >8.0 mmol/L, respectively. The prevalence of raised lactate levels (>5 mmol/L) was greater in children with malaria than in children with nonmalarial febrile illness (P < .001) although the associated mortality was greater in slide-negative children. CONCLUSIONS: POC lactate measurement can contribute to the assessment of children admitted to hospital with febrile illness and can also create an opportunity for more hospitals in resource-poor settings to participate in clinical trials of interventions to reduce mortality associated with hyperlactatemia

A randomized comparison of two anemia treatment regimens in Tanzanian children.

We used a prospective, open-label randomized trial to evaluate two treatment regimens in Tanzanian children two months to four years of age presenting to a hospital with a packed cell volume (PCV) < 25%. Treatment was either standard (14 days of ferrous sulfate and an antimalarial) or extended (three months of ferrous sulfate and three antimalarial treatments). The prevalence of anemia was measured two weeks after completion of treatment and six months after recruitment. Two weeks after completing treatment, the prevalence of PCV < 33% was 58% in the standard treatment arm and 44% in the extended treatment group (P = 0.04), and the mean PCV was significantly higher in the extended treatment arm (32.1%, SD = 4.5% versus 30.8%, SD = 4.9%; P = 0.031). However, there was no difference in the prevalence of PCV < 25% in the first survey, and the benefits of extended therapy were only apparent six months after recruitment in children compliant with the extended treatment (odds ratio of PCV < 25% = 0.16, P = 0.06). Compliance was satisfactory in only 39% (82 of 209) of the children in the first week of treatment. Extending the duration of therapy and improving compliance may have health benefits for anemic children in malaria-endemic settings

Age interactions in the development of naturally acquired immunity to Plasmodium falciparum and its clinical presentation

Background Naturally acquired malaria immunity has many determinants and, in the absence of immunological markers of protection, studies assessing malaria incidence through clinical endpoints remain an approach to defining immunity acquisition. We investigated the role of age in disease incidence and the effects of chemoprophylaxis on clinical immunity development to Plasmodium falciparum during a randomised controlled trial. Methods and Findings A total of 415 Tanzanian infants were randomly assigned to receive weekly malaria prophylaxis with Deltaprim (3.125 mg of pyrimethamine plus 25 mg of dapsone) or placebo between the ages of 2 and 12 mo. Children were followed up until 4 y of age. Uncomplicated febrile malaria, severe malaria, and anaemia morbidity were assessed through hospital-based passive surveillance. Compared with the group of control participants, there was a marked reduction in the incidence of clinical malaria, severe malaria, and anaemia in the group of children who had received chemoprophylaxis during the first year of life. After discontinuing the intervention, there was a significant increase in the incidence of clinical malaria for 2 y. The cumulative rates of clinical malaria, by age 4 y, were slightly higher in the group of children who had previously received chemoprophylaxis: 3.22 episodes versus 3.02 episodes in the group of control participants; rate difference 0.20 (95% confidence interval [CI]: −0.21 to 0.59). By age 4 y, the cumulative rates of severe malaria, however, were slightly lower in chemosuppressed children (0.47 versus 0.59) (rate difference −0.12 [95% CI: −0.27 to 0.03]). The number of episodes of anaemia was also slightly lower in chemosuppressed children by age 4y: 0.93 episodes (95% CI: 0.79 to 0.97) versus 1.12 episodes in the group of control participants (95% CI: 0.97 to 1.28) (rate difference −0.19 [95% CI: −0.40 to 0.01]), respectively. Conclusions Reducing exposure to P. falciparum antigens through chemoprophylaxis early in life can delay immunity acquisition. Infants appear to acquire immunity faster than older children, but have a higher risk of developing severe forms of malaria and anaemia. These findings provide insight on the interplay between immunity and exposure-reduction interventions

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

BACKGROUND Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. METHODS A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. FINDINGS Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). INTERPRETATION The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.Financial support for IMPACT-Tz came primarily from CDC, the U.S. Agency for International Development and the Wellcome Trust

Epidemiology of Malaria in an Area Prepared for Clinical Trials in Korogwe, North-eastern Tanzania.

Site preparation is a pre-requesite in conducting malaria vaccines trials. This study was conducted in 12 villages to determine malariometric indices and associated risk factors, during long and short rainy seasons, in an area with varying malaria transmission intensities in Korogwe district, Tanzania. Four villages had passive case detection (PCD) of fever system using village health workers. Four malariometric cross-sectional surveys were conducted between November 2005 and May 2007 among individuals aged 0-19 years, living in lowland urban, lowland rural and highland strata. A total of 10,766 blood samples were collected for malaria parasite diagnosis and anaemia estimation. Blood smears were stained with Giemsa while haemoglobin level was measured by HaemoCue. Socio-economic data were collected between Jan-Apr 2006. Adjusting for the effect of age, the risk of Plasmodium falciparum parasitaemia was significantly lower in both lowland urban, (OR = 0.26; 95%CI: 0.23-0.29, p < 0.001) and highlands, (OR = 0.21; 95%CI: 0.17-0.25, p < 0.001) compared to lowland rural. Individuals aged 6-9 years in the lowland rural and 4-19 years in both lowland urban and highlands had the highest parasite prevalence, whilst children below five years in all strata had the highest parasite density. Prevalence of splenomegaly and gametocyte were also lower in both lowland urban and highlands than in lowland rural. Anaemia (Hb <11 g/dl) prevalence was lowest in the lowland urban. Availability of PCD and higher socio-economic status (SES) were associated with reduced malaria and anaemia prevalence. Higher SES and use of bed nets in the lowland urban could be the important factors for low malaria infections in this stratum. Results obtained here were used together with those from PCD and DSS in selecting a village for Phase 1b MSP3 vaccine trial, which was conducted in the study area in year 2008

Varying efficacy of intermittent preventive treatment for malaria in infants in two similar trials: public health implications.

BACKGROUND\ud \ud Intermittent preventive treatment (IPTi) with sulphadoxine-pyrimethamine (SP) in infants resulted in different estimates of clinical malaria protection in two trials that used the same protocol in Ifakara, Tanzania, and Manhiça, Mozambique. Understanding the reasons for the discrepant results will help to elucidate the action mechanism of this intervention, which is essential for rational policy formulation.\ud \ud METHODS\ud \ud A comparative analysis of two IPTi trials that used the same study design, follow-up, intervention, procedures and assessment of outcomes, in Tanzania and Mozambique was undertaken. Children were randomised to receive either SP or placebo administered 3 times alongside routine vaccinations delivered through the Expanded Program on Immunisation (EPI). Characteristics of the two areas and efficacy on clinical malaria after each dose were compared.\ud \ud RESULTS\ud \ud The most relevant difference was in ITN's use ; 68% in Ifakara and zero in Manhiça. In Ifakara, IPTi was associated with a 53% (95% CI 14.0; 74.1) reduction in the risk of clinical malaria between the second and the third dose; during the same period there was no significant effect in Manhiça. Similarly, protection against malaria episodes was maintained in Ifakara during 6 months after dose 3, but no effect of IPTi was observed in Manhiça.\ud \ud CONCLUSION\ud \ud The high ITN coverage in Ifakara is the most likely explanation for the difference in IPTi efficacy on clinical malaria. Combination of IPTi and ITNs may be the most cost-effective tool for malaria control currently available, and needs to be explored in current and future studies.\ud \ud TRIAL REGISTRATION\ud \ud Manhiça study registration number: NCT00209795Ifakara study registration number: NCT88523834

Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study.

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control