BackgroundMalaria is the commonest cause of childhood morbidity in Western Kenya with varied heamatological consequences. The t study sought to elucidate the haemotological changes in children infected with malaria and their impact on improved diagnosis and therapy of childhood malaria.MethodsHaematological parameters in 961 children, including 523 malaria-infected and 438 non-malaria infected, living in Kisumu West District, an area of malaria holoendemic transmission in Western Kenya were evaluated.ResultsThe following parameters were significantly lower in malaria-infected children; platelets, lymphocytes, eosinophils, red blood cell count and haemoglobin (Hb), while absolute monocyte and neutrophil counts, and mean platelet volume (MPV) were higher in comparison to non-malaria infected children. Children with platelet counts of <150,000/uL were 13.8 times (odds ratio) more likely to have malaria. Thrombocytopaenia was present in 49% of malaria-infected children and was associated with high parasitaemia levels, lower age, low Hb levels, increased MPV and platelet aggregate flag. Platelet aggregates were more frequent in malaria-infected children (25% vs. 4%, p<0.0001) and associated with thrombocytopaenia rather than malaria status.ConclusionChildren infected with Plasmodium falciparum malaria exhibited important changes in some haematological parameters with low platelet count and haemoglobin concentration being the two most important predictors of malaria infection in children in our study area. When used in combination with other clinical and microscopy, these parameters could improve malaria diagnosis in sub-patent cases.

Following a marked decline in the efficacy in vivo of mefloquine between 1990 and 1994, a combination of artesunate (4 mg/kg/d for 3 d) and mefloquine (25 mg/kg) has been used as first line treatment of uncomplicated falciparum malaria in camps for displaced persons located along the north-western border of Thailand. Antimalarial drug susceptibility of fresh isolates of Plasmodium falciparum from this population was evaluated using a radioisotope microdilution assay between 1995 and 1999. In total, 268 isolates were collected, of which 189 were from primary infections and 79 from recrudescent infections. The geometric mean 50% inhibitory concentration (IC50) values from primary infections were: dihydroartemisinin 1.2 ng/mL, artesunate 1.6 ng/mL, artemether 4.8 ng/mL, atovaquone 0.4 ng/mL, lumefantrine 32 ng/mL, chloroquine 149 ng/mL, quinine 354 ng/mL, mefloquine 27 ng/mL and halofantrine 4.1 ng/mL. A significant positive correlation was found between the susceptibility in vitro to artesunate and quinine (r = 0.43, P < 0.001), mefloquine (r = 0.46, P < 0.001), and halofantrine (r = 0.51, P < 0.001). These levels of resistance in vitro are among the highest reported and confirm continuing high level multidrug resistance in this area. Despite intensive use of the combination between 1995 and 1999 there has been a significant improvement in mefloquine sensitivity (P < 0.001) and artesunate sensitivity (P < 0.001). This supports observations in vivo that the combination of artesunate and mefloquine has reversed the previous decline in mefloquine sensitivity.

Single Nucleotide Polymorphisms (SNPs) in the Pfmdr1, and Pfcrt, genes of Plasmodium falciparum may confer resistance to a number of anti-malaria drugs. Pfmdr1 86Y and haplotypes at Pfcrt 72-76 have been linked to chloroquine (CQ) as well as amodiaquine (AQ) resistance. mefloquine (MQ) and lumefantrine (LU) sensitivities are linked to Pfmdr1 86Y. Additionally, Pfcrt K76 allele carrying parasites have shown tolerance to LU. We investigated the association between Pfmdr1 86/Pfcrt 72-76 and P. falciparum resistance to CQ, AQ, MQ and LU using field samples collected during 2008–2011 from malaria endemic sites in western Kenya. Genomic DNA from these samples was genotyped to examine SNPs and haplotypes in Pfmdr1 and Pfcrt respectively. Additionally, immediate ex vivo and in vitro drug sensitivity profiles were assessed using the malaria SYBR Green I fluorescence-based assay. We observed a rapid but steady percent increase in wild-type parasites with regard to both Pfmdr1 and Pfcrt between 2008 and 2011 (p<0.0001). Equally, a significant reciprocate decrease in AQ and CQ median IC50 values occurred (p<0.0001) during the same period. Thus, the data in this study point to a significantly rapid change in parasite response to AQ and CQ in the study period. This may be due to releasing of drug pressure on the parasite from reduced use of AQ in the face of increased Artemisinin (ART) Combination Therapy (ACT) administration following the intervention of the Global Fund in 2008. LU has been shown to select for 76K genotypes, thus the observed increase in 76K genotypes coupled with significant cross resistance between LU and MQ, may herald emergence of tolerance against both drugs in future.

Tafenoquine doses as low as a single 600-mg dose may be useful for prevention of relapse of P. vivax malaria in Thailand.

WR 238605 is an 8-aminoquinoline developed for the radical cure of Plasmodium vivax. Forty-four P. vivax-infected patients were randomly assigned to 1 of 4 treatment regimens: 3 groups received a blood schizonticidal dose of chloroquine followed by WR 238605: group A (n=15) received 300 mg daily for 7 days; group B (n=11), 500 mg daily for 3 days, repeated 1 week after the initial dose; group C (n=9), 1 dose of 500 mg. A fourth group (D; n=9) received chloroquine only. Among patients who completed 2-6 months of follow-up (n=23), there was 1 relapse in group B (day 120) and 1 in group C (day 112). Among patients treated with chloroquine only, there were 4 relapses (days 40, 43, 49, and 84). WR 238605 was safe, well tolerated, and effective in preventing P. vivax relapse.

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Mycobacterium ulcerans is an emerging infection that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU). Bone lesions may include reactive osteitis or osteomyelitis beneath skin lesions, or metastatic osteomyelitis from lymphohematogenous spread of M. ulcerans. Pathogenesis is related to a necrotizing and immunosuppressive toxin produced by M. ulcerans, called mycolactone. The incidence of BU is highest in children up to 15 years old, and is a major public health problem in endemic countries due to disabling scarring and destruction of bone. Most patients live in West Africa, but the disease has been confirmed in at least 30 countries. Treatment options for BU are antibiotics and surgery. BCG vaccination provides short-term protection against M. ulcerans infection and prevents osteomyelitis. HIV infection may increase risk for BU, and renders BU highly aggressive. Unlike leprosy and tuberculosis, BU is related to environmental factors and is thus considered non-communicable. The most plausible mode of transmission is by skin trauma at sites contaminated by M. ulcerans. The reemergence of BU around 1980 may be attributable to environmental factors such as deforestation, artificial topographic alterations and increased manual agriculture of wetlands. The first cultivation of M. ulcerans from nature was reported in 2008.