John N. Waitumbi

Outpatient Upper Respiratory Tract Viral Infections in Children with Malaria Symptoms in Western Kenya

A cross-sectional study was performed in children 5 through 10 years of age presenting to outpatient clinics in Nyanza Province, Kenya, in which nasal swab and blood specimens were collected during the high malaria transmission season. Patients presenting with malaria-like symptoms within 4 days of fever onset were enrolled in the study. Plasmodium parasitemia was determined by blood smear microscopy. Nasal swabs were screened for a panel of respiratory viruses by polymerase chain reaction. Influenza A, rhinoviruses, and other respiratory viruses were detected in 18%, 26%, and 12% of 197 specimens, respectively. Four of 36 patients with influenza A had a positive malaria blood slide, compared with 20 of 52 patients with rhinovirus. A significant burden of disease caused by influenza A in febrile children during the study period was observed, highlighting the need for further research into the burden of influenza disease in regions where malaria is holoendemic.

Evaluation of recurrent parasitemia after artemether-lumefantrine treatment for uncomplicated malaria in children in western Kenya.

From April 2005 to April 2006, a phase 2 malaria vaccine trial in Kenya enrolled 400 children aged 12-47 months. Each received mixed supervised and unsupervised artemether-lumefantrine for uncomplicated malaria, using a standard six-dose regimen, by weight. Children were followed for detection of parasitemia and clinical malaria. A median of two negative malaria blood films occurred during every recurrent parasitemia (RP) episode, suggesting reinfection over late recrudescence. Median time to RP after starting artemether-lumefantrine was 37 days (36-38). Of 2,020 evaluable artemether-lumefantrine treatments, there were no RPs in 99% by day 14, 71% by day 28, and 41% by day 42. By World Health Organization standards, 71% of treatment courses had adequate responses. Although recrudescence in some cannot be ruled out, our cohort had a shorter median time to RP compared with other artemether-lumefantrine treatment studies. This underscores patient counseling on completing all treatment doses for optimal protection from RP.

Phase 2a, Open-Label, 4-Escalating-Dose, Randomized Multicenter Study Evaluating the Safety and Activity of Ferroquine (SSR97193) Plus Artesunate, versus Amodiaquine Plus Artesunate, in African Adult Men with Uncomplicated Plasmodium falciparum Malaria.

Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator. After a 2:1 randomization (block size three, equating to N = 12 for each ferroquine dose and N = 6 for each of four amodiaquine comparator groups) patients received daily for three consecutive days, either ferroquine + AS (200 mg/day) or amodiaquine (612 mg/day) + AS (200 mg/day). Safety, electrocardiograms, parasite clearance times, efficacy, and pharmacokinetics were assessed to day 28. Seventy-two patients were randomized. Ferroquine + AS showed generally mild increases (Grade 1 toxicity) in alanine aminotransferase (ALT) levels with a dose trend starting at 400 mg. There were two Grade 2 ALT events: one patient receiving 200 mg (3.8 upper limit of normal [ULN], day 7) and one receiving 600 mg (3.3 ULN, day 14), both without increased bilirubin. One ferroquine 100 mg + AS patient after one dose was withdrawn after developing a QTcF interval prolongation > 60 milliseconds over baseline. Parasitemias in all patients cleared quickly, with no recurrence through day 28. Hepatic, as well as cardiac, profiles should be monitored closely in future trials. (ClinicalTrials.gov: NCT00563914).

Females of HbAS genotype have reduced concentration of the malaria protective deoxyhemoglobin S than males

The quantity of the intra-erythrocytic deoxyhemoglobin S (Hb S) affects the level of protection against malaria and also the sickling phenomenon. This study reports on significantly lower concentration of Hb S in females than males. Data came from 350 children, aged 12–47 months who participated in a phase 2b malaria vaccine trial. Hemoglobinopathy and G6PD deficiency typing was necessary to ascertain equal representation of these malaria protective traits across the vaccine cohorts. Hemoglobin types (HbAA, HbAS) and % Hb S were evaluated by HPLC. Alpha thalassemia (alpha-thal) and G6PD genotypes were evaluated by PCR. The overall prevalence for HbAS was 20%, 46% for 3 alpha genes and 10% for 2 alpha genes and 14% for G6PD A-. More females of HbAS/αα/αα genotype had low Hb S than males and had mean % Hb S of 37.5% ± 5.4 SD, compared to 42.0% ± 2.5 SD in males of same genotype (P = 0.018). Consistent with reduction of the malaria protective Hb S in females, parasite load in females was nearly twice that of males but the difference was not statistically significant. The X-chromosome linked G6PD deficiency did not influence the level of Hb S. We conclude that, the low Hb S in these females explains the resultant higher malaria parasite load. We speculate that the low Hb S in females could also explain observations suggesting that the sickling phenomenon tends to be less severe in females than males.

Zika Virus Screening in the Kenyan Olympic Team Attending the 2016 Olympic Games in Brazil

The 2016 Olympic Games happened at the time of heightened fears of Zika virus (ZIKV) that was causing microcephaly in newborns in Brazil. To avert or track introduction of ZIKV in Kenya, the Ministry of Health developed a public health response that involved screening of the Kenyan contingent before and after traveling to Brazil. Of the 92 team members that were screened, all but one tested negative for ZIKV IgM and IgG. The sero-positive individual had high IgM serum titers before and after travel to Brazil. When tested for potential antibody cross-reactivity to other flaviviruses that have been reported in Kenya, the sample showed high IgM cross-reactivity to West Nile, Tick-Borne Encephalitis and Yellow Fever Virus. Our data support the low risk predictions of acquiring ZIKV that were made before the Games and will help inform risk assessments for personnel traveling to endemic regions under similar circumstances in the future.