There is no information and therefore no consensus on how chloroquine should be administered to persons with severe malaria. Although widely considered dangerous, parenteral chloroquine is extensively used. We studied the acute disposition and toxicity of intravenous (iv), intramuscular (im), subcutaneous (sc), and oral chloroquine in 60 adult Zambian patients hospitalized with falciparum malaria. Plasma concentration profiles after parenteral administration were characterized by wide fluctuations between peak and trough values. Absorption of im and sc chloroquine was rapid, with a median time to peak concentration of 30 min and a peak plasma concentration five times higher than after oral administration. The pharmacokinetic data suggest that the acute toxicity of parenteral chloroquine is related to transiently high concentrations in blood and result from incomplete distribution out of a relatively small central compartment. Parenteral chloroquine may be administered safely by simply giving smaller, more-frequent doses than are currently used or, in the case of iv administration, by using continuous infusion.
1315We are grateful to Dr J Stevenson and Dr E C Gordon Smith for allowing us to report this case.'Perillo RP, Pohl DA, Roodman ST, Tsai CC. Acute non A non B hepatitis with serum sickness-like syndrome and aplastic anaemia. JAMA 1981 ;245:494-6 Conversiotn: SI to traditional iuits-viscosity of plasma and whole blood: I mPa s I cP.30"', increase in fetal blood viscosity, this rise being compounded of a 120%increase in packed cell volume and an 18% fall in erythrocyte deformability.Neither plasma viscosity nor plasma fibrinogen values were altered. The mean birth weight was 318 g lower in infants born to smoking mothers. CommentMaternal cigarette smoking in pregnancy results in changes in fetal blood viscosity and its major determinants similar to those described in non-pregnant adult smokers.3 When adult smokers become pregnant the large physiological variations in blood viscosity factors obscure the effects of smoking in maternal blood5 but not so in the fetus. In the extensive capillary microcirculation of the fetal placental villi, raised blood viscosity and reduced erythrocyte deformability would be apt to reduce blood flow significantly in accordance with Poiseuille's law. Reduced intravillous perfusion would combine with reduced intervillous blood flow on the maternal side of the placenta, owing to the effects of nicotine, and with the already reduced oxygen availability in both maternal and fetal blood, to cause fetal hypoxia stimulating fetal erythropoiesis with a further increase in blood viscosity leading to a vicious circle of decreasing flow and further hypoxia. This study indicates a new pathogenic pathway for the deleterious effects of maternal cigarette smoking on fetal growth and development in pregnancy. Recently, chloroquine resistant Plasmodium falciparum has been acquired in east Africa by white visitors.' 2 We have carried out more than 25 successful in vitro macrotests, 15 in vitro microtests using capillary blood specimens, and 130 in vivo tests on the susceptibility of P falciparum in Zambia to chloroquine and to the new antimalarial drug mefloquine.3-5 In the in vivo tests the patients were observed in an environment free of mosquitoes for 28-63 days after they developed malaria. Our results showed that P falciparum in Zambia is generally sensitive to standard doses of chloroquine or mefloquine.Here, however, we report perhaps the first proved case of chloroquine resistant Pfalciparum in an African living in Africa.Case report A 26 year old Zambian staff nurse developed clinical malaria, which was confirmed microscopically to be due to asexual P falciparum, one month after she had moved to a village 1000 km north east of Ndola. She was treated on 10 June 1982 with two doses of 200 mg chloroquine intramuscularly at an interval of eight hours. She refused a further injection of chloroquine the next day and instead took 600 mg amodiaquine by mouth. Her clinical condition improved for four days, during which time she returned to Ndola. For the next 10 days she felt slightly unwell with feve...
Background People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count. Results We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28–42) years and 31(25–36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465–702.5 cells/mm3] vs 345 [157–483 cell/mm3] in HIV negative vs HIV positive respectively p = <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827–23,686 pg/ml] vs. 9,508 [5,514–15,008 pg/ml], respectively; p = 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3 for both cohorts. 21,953 [8,990–24,206 pg/ml] vs 9,505 [5,400–15,313 pg/ml], p value = 0.0585 in patients with CD4 count < 500 cell/mm3 and 13,168 [7,087–22,584 pg/ml] vs 10,413 [7,397–14,806 pg/ml], p value = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36–0.72; p < 0.0001) and r = 0.48 (95% CI 0.15–0.68; p = 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0–0.28] vs 0.007 [0–0.32] respectively; p = 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99, p value 0.007. Conclusions This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.
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