Plasma zinc concentrations are depressed during the acute phase response in children with falciparum malaria

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (\u3c9.2 μmol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P \u3c 0.0001) and the degree of parasitemia (r = -0.19, P \u3c 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response. © 2005 American Society for Nutritional Sciences

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possibl

Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment

Effect of zinc on the treatment of Plasmodium falciparum malaria in children: A randomized controlled trial

Background: Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria. Objective: The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken. Design: Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and ≥ 2000 asexual forms of Plasmodium falciparum/μL in a thick blood smear received chloroquine and were randomly assigned to receive zinc (20 mg/d for infants, 40 mg/d for older children) or placebo for 4 d. Results: There was no effect of zinc on the median time to reduction of fever (zinc group: 24.2 h; placebo group: 24.0 h; P = 0.37), a ≥75% reduction in parasitemia from baseline in the first 72 h in 73.4% of the zinc group and in 77.6% of the placebo group (P = 0.11), and no significant change in hemoglobin concentration during the 3-d period of hospitalization and the 4 wk of follow-up. Mean plasma zinc concentrations were low in all children at baseline (zinc group: 8.54 ± 3.93 μmol/L; placebo group: 8.34 ± 3.25 μmol/L), but children who received zinc supplementation had higher plasma zinc concentrations at 72 h than did those who received placebo (10.95 ± 3.63 compared with 10.16 ± 3.25 μmol/L, P \u3c 0.001). Conclusion: Zinc does not appear to provide a beneficial effect in the treatment of acute, uncomplicated falciparum malaria in preschool children

Estimating the economic and social consequences for patients diagnosed with human African trypanosomiasis in Muchinga, Lusaka and Eastern Provinces of Zambia (2004-2014)

Abstract Background Acute human African trypanosomiasis (rHAT) caused by Trypanosoma brucei rhodesiense is associated with high mortality and is fatal if left untreated. Only a few studies have examined the psychological, social and economic impacts of rHAT. In this study, mixed qualitative and quantitative research methods were used to evaluate the socio-economic impacts of rHAT in Mambwe, Rufunsa, Mpika and Chama Districts of Zambia. Methods Individuals diagnosed with rHAT from 2004 to 2014 were traced using hospital records and discussions with communities. Either they, or their families, were interviewed using a structured questionnaire and focus group discussions were conducted with affected communities. The burden of the disease was investigated using disability adjusted life years (DALYs), with and without discounting and age-weighting. The impact of long-term disabilities on the rHAT burden was also investigated. Results Sixty four cases were identified in the study. The majority were identified in second stage, and the mortality rate was high (12.5%). The total number of DALYs was 285 without discounting or age-weighting. When long-term disabilities were included this estimate increased by 50% to 462. The proportion of years lived with disability (YLD) increased from 6.4% to 37% of the undiscounted and un-age-weighted DALY total. When a more active surveillance method was applied in 2013–2014 the cases identified increased dramatically, suggesting a high level of under-reporting. Similarly, the proportion of females increased substantially, indicating that passive surveillance may be especially failing this group. An average of 4.9 months of productive time was lost per patient as a consequence of infection. The health consequences included pain, amnesia and physical disability. The social consequences included stigma, dropping out of education, loss of friends and self-esteem. Results obtained from focus group discussions revealed misconceptions among community members which could be attributed to lack of knowledge about rHAT. Conclusions The social and economic impact of rHAT on rural households and communities is substantial. Improved surveillance and strengthening of local medical services are needed for early and accurate diagnosis. Disease prevention should be prioritised in communities at risk of rHAT, and interventions put in place to prevent zoonotic disease spill over from domestic animals and wildlife. Supportive measures to mitigate the long-term effects of disability due to rHAT are needed

Helminths and HIV infection: epidemiological observations on immunological hypotheses

Parasitic helminths have co-evolved with the mammalian immune system. Current hypotheses suggest that immunological stimulation in the presence of helminths is balanced by immuno-regulation and by the broad spectrum of mechanisms possessed by helminths for countering the host immune response. The degree to which this balance is perfected, and the mechanisms by which this is achieved, vary between helminth species; we suggest that this is reflected not only in the degree of pathology induced by helminths but also in a variety of relationships with HIV infection and HIV disease. Available epidemiological data regarding interactions between helminths and HIV are largely observational; results are variable and generally inconclusive. Well designed, controlled intervention studies are required to provide definitive information on the species-specific nature of these interactions and on the advantages, disadvantages and optimal timing of de-worming in relation to HIV infection

Treatment of Helminth Co-Infection in Individuals with HIV-1: A Systematic Review of the Literature

Many people living in areas of the world most affected by the HIV/AIDS pandemic are also exposed to other common infections. Parasitic infections with helminths (intestinal worms) are common in Africa and affect over half of the population in some areas. There are plausible biological reasons why treating helminth infections in people with HIV may slow down the progression of HIV to AIDS. Thus, treating people with HIV for helminths in areas with a high prevalence of both HIV and helminth infections may be a feasible strategy to help people with HIV delay progression of their disease or initiation of antiretroviral therapy. After a comprehensive review of the available literature, we conclude that there is not enough evidence to determine whether treating helminth infections in people with HIV is beneficial

Treating cofactors can reverse the expansion of a primary disease epidemic

<p>Abstract</p> <p>Background</p> <p>Cofactors, "nuisance" conditions or pathogens that affect the spread of a primary disease, are likely to be the norm rather than the exception in disease dynamics. Here we present a "simplest possible" demographic model that incorporates two distinct effects of cofactors: that on the transmission of the primary disease from an infected host bearing the cofactor, and that on the acquisition of the primary disease by an individual that is not infected with the primary disease but carries the cofactor.</p> <p>Methods</p> <p>We constructed and analyzed a four-patch compartment model that accommodates a cofactor. We applied the model to HIV spread in the presence of the causal agent of genital schistosomiasis, <it>Schistosoma hematobium</it>, a pathogen commonly co-occurring with HIV in sub-Saharan Africa.</p> <p>Results</p> <p>We found that cofactors can have a range of effects on primary disease dynamics, including shifting the primary disease from non-endemic to endemic, increasing the prevalence of the primary disease, and reversing demographic growth when the host population bears only the primary disease to demographic decline. We show that under parameter values based on the biology of the HIV/<it>S. haematobium </it>system, reduction of the schistosome-bearing subpopulations (e.g. through periodic use of antihelminths) can slow and even reverse the spread of HIV through the host population.</p> <p>Conclusions</p> <p>Typical single-disease models provide estimates of future conditions and guidance for direct intervention efforts relating only to the modeled primary disease. Our results suggest that, in circumstances under which a cofactor affects the disease dynamics, the most effective intervention effort might not be one focused on direct treatment of the primary disease alone. The cofactor model presented here can be used to estimate the impact of the cofactor in a particular disease/cofactor system without requiring the development of a more complicated model which incorporates many other specific aspects of the chosen disease/cofactor pair. Simulation results for the HIV/<it>S. haematobium </it>system have profound implications for disease management in developing areas, in that they provide evidence that in some cases treating cofactors may be the most successful and cost-effective way to slow the spread of primary diseases.</p