Chloroquine treatment of falciparum malaria in an area of Kenya of intermediate chloroquine resistance

106 children aged 1-10 years who had pure Plasmodium falciparum infections and temperatures greater than or equal to 38 degrees C were treated with chloroquine base, 25 mg/kg body weight. 29% of the infections were sensitive in vivo, 41% recurred within 4 weeks (RI), 26% were RII resistant, and 4% were RII resistant. Rieckmann micro in vitro tests were successful in 64% of isolates obtained from these children; 63% were resistant to chloroquine. In 58 paired isolates obtained before and after treatment, the level of chloroquine sensitivity was lower in the parasites persisting or recurring after treatment. All children except 2 of the 4 with RIII resistance became afebrile an average of 1.4 d after starting treatment and their other symptoms resolved in an average of 1.8 d. By day 28, 57% of the children with RI resistance and 78% of those with RII resistance had recurrence of fever and other symptoms, compared with 19% of children with sensitive infections. No relationship was observed between the clinical or parasitological response and age, nutritional status, haematocrit, splenomegaly, presence of sickle-cell trait, or seropositivity to malaria by enzyme-linked immunosorbent assay. The study demonstrates that, in most children with malaria in an area of intermediate chloroquine resistance, fever and other symptoms resolve at least temporarily when treated with chloroquine.     

Posterior spinal cord block: a dosimetric study

To determine the optimal width of a midline posterior spinal block (MPSB) (to avoid delivering too great a dose to the cord and too small a dose to adjacent tissue), the authors determined with magnetic resonance (MR) imaging normal ranges of cord depth and width and correlated them with film dosimetric data. In 59 randomly selected patients there was a wide range for both depth and width. The average depths of the anterior and posterior surfaces of the cord were 6.7 cm +/- 1.4 and 5.4 cm +/- 1.3, respectively. The average cord width was 1.6 cm +/- 0.4. Optimal cord block width as a function of cord width was determined for a 6-MV photon beam. The optimal cord block width at the surface (half-value layer [HVL] thickness = 6) varied from 1.5 to 3.0 cm for cord widths of 0.8-2.4 cm, which correspond to two standard deviations from the average. There was no significant dependence on depth of the cord. For optimal treatment outcome, the MPSB width may have to be determined for each patient individually.     

Ultrasonography and computed tomography of inflammatory abdominal wall lesions

Twenty-four patients with inflammatory lesions of the abdominal wall were examined by ultrasonography. Nine of these patients underwent computed tomographic (CT) scanning as well. Both ultrasonography and CT clearly delineated the exact location and extent of abdominal wall abscesses. Abscesses were easily differentiated from cellulitis or phlegmon with ultrasound. The peritoneal line was more clearly delineated on ultrasonograms than on CT scans; abscesses were also more distinct on the ultrasonograms because of their low echogenicity compared with the surrounding structures. Gas bubbles, fat density with specific low attenuation values, and underlying inflamed bowel loops in obese patients with Crohn's disease were better delineated by CT.     

Increasing prevalence of multidrug-resistant non-typhoidal salmonellae, Kenya, 1994-2003

Over the last decade there has been a steady increase in the proportion of multidrug resistance among non-typhoidal salmonellae (NTS) isolated from adult patients with bacteraemia in Kenya. The prevalence of NTS multiply resistant to all commonly available drugs including ampicillin, streptomycin, co-trimoxazole, chloramphenicol and tetracycline rose from 31% in 1994 to 42% at present, with concomitantly higher MICs of each drug. Resistance is encoded on large self-transferable 100-110 kb plasmids. Pulsed field gel electrophoresis of XbaI and SpeI digested chromosomal DNA revealed three main digest patterns for Salmonella enterica serotype Typhimurium and two main patterns for Salmonella enterica serotype Enteritidis. Although the genotypes of NTS remained fairly stable over the last decade, the large increase in MICs of all commonly used drugs and increased MICs of ciprofloxacin, poses a major challenge for treatment of invasive NTS infection.     

Detailed clinical and ultrasound examination of children and adolescents in a Schistosoma mansoni endemic area in Kenya: hepatosplenic disease in the absence of portal fibrosis

Hepatosplenic schistosomiasis involving organomegaly, portal fibrosis and portal hypertension has been observed in autopsy studies. Here, we have tested the hypothesis that hepatosplenic disease including organomegaly and markers of increased portal pressure can occur in school aged children in the absence of fibrosis. A case-only study of 96 children aged 7-20 years defined by ultrasound detectable hepatomegaly was undertaken in Makueni district, Kenya. A novel method of clinical examination that involved a consensus scoring by three or four examiners was used to classify children as presenting with severe or moderate hepatosplenic disease after palpation of livers and spleens. Ultrasound examination of livers and spleens was based on the Niamey protocol. Clinical measurements included spleen enlargement along the mid-clavicular and mid-axillary lines, liver enlargement along the mid-sternal (MSL) and mid-clavicular lines, as well as organ consistency. The clinical examination indicated that 9% and 60% of the children had severe or moderate hepatosplenomegaly, respectively. Amongst egg-positive children, all clinical measurements, except MSL liver enlargement, correlated with egg count, as did portal vein diameter, spleen length and liver length measured by ultrasound. Peri-portal fibrosis was not observed in any child, whereas 28% of the children were classified as having increased portal pressure according to World Health Organization criteria. There was no effect of malaria parasitaemia or hepatitis seropositvity on any of the observed parameters. These results indicate that hepatosplenic disease in school-aged children attributable to S. mansoni infection, involving hepatosplenomegaly and increased portal vein diameter, can occur in the absence of peri-portal fibrosis.     

Quantile regression for the statistical analysis of immunological data with many non-detects

Background

Hemolytic uremic syndrome (HUS) leading to acute kidney failure, is a condition linked to the production of primarily Shiga toxin 2 (Stx2) by some E. coli serotypes. We have previously shown that Stx2 A subunit-specific human monoclonal antibody (HuMAb) 5C12, and B subunit-specific HuMAb 5H8 inhibit cultured cell death, and protect mice and piglets from fatal Stx2-intoxication. We have also shown that 5H8 blocks binding of Stx2 to its cell-surface receptor globotriaosyl ceramide (Gb₃), whereas Stx2 when complexed with 5C12 binds Gb₃ with higher affinity than Stx2. The mechanism by which 5C12 neutralizes Stx2 in vitro involves trapping of Stx2 in the recycling endosomes and releasing it into the extracellular environment. Because of the clinical implications associated with the formation of Stx2/antibody complexes and the potential for trapping and clearance through a severely damaged kidney associated with HUS, we investigated the likely site(s) of Stx2/antibody localization and clearance in intoxicated mice treated with antibody or placebo.

Results

Mice were injected with radiolabeled Stx2 (¹²⁵I-Stx2) 4 hours after administration of 5C12, 5H8, or phosphate buffered saline (PBS) and the sites of localization of labeled Stx2, were investigated 3, 24 and 48 hours later. The liver recorded statistically much higher concentrations of labeled Stx2 for groups receiving 5C12 and 5H8 antibodies after 3, 24 and 48?hours, as compared with the PBS group. In contrast, highest levels of labeled Stx2 were detected in the kidneys of the PBS group at all 3 sampling times. Mice receiving either of the two HuMAbs were fully protected against the lethal effect of Stx2, as compared with the fatal outcome of the control group.

Conclusions

The results suggest that HuMAbs 5C12 and 5H8 promoted hepatic accumulation and presumably clearance of toxin/antibody complexes, significantly diverting Stx2 localization in the kidneys, the target of Stx2 and the cause of HUS. This is in contrast to the fatal outcome of the control group receiving PBS. The results also confirm earlier observations that both HuMAbs are highly and equally protective against Stx2 intoxication in mice.     

Challenges of establishing the correct diagnosis of outbreaks of acute febrile illnesses in Africa: the case of a likely Brucella outbreak among nomadic pastoralists, northeast Kenya, March-July 2005

An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed.     

In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya

Objectives  To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya.
Methods  Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6–59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria.
Results  The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrolment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences.
Conclusion  Although artemether-lumefantrine (Coartem^®) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an effective alternative to Coartem^® in western Kenya. Continued amodiaquine monotherapy in the private sector may jeopardise the future use of amodiaquine-artesunate as an alternative artemisinin-based combination therapy.