Correlation Between Malaria-Specific Antibody Profiles and Responses to Artemisinin Combination Therapy for Treatment of Uncomplicated Malaria in Western Kenya.

BACKGROUND: The impact of preexisting immunity on the efficacy of artemisinin combination therapy must be examined to monitor resistance, and for implementation of new treatment strategies. METHODS: Serum samples obtained from a clinical trial in Western Kenya randomized to receive artemether-lumefantrine (AL) or artesunate-mefloquine (ASMQ) were screened for total immunoglobulin G against preerythrocytic and erythrocytic antigens. The association and correlation between different variables, and impact of preexisting immunity on parasite slope half-life (t½) was determined. RESULTS: There was no significant difference in t½, but the number of individuals with lag phase was significantly higher in the AL than in the ASMQ arm (29 vs 13, respectively; P < .01). Circumsporozoite protein-specific antibodies correlate positively with t½ (AL, P = .03; ASMQ, P = .09), but negatively with clearance rate in both study arms (AL, P = .16; ASMQ, P = .02). The t½ correlated negatively with age in ASMQ group. When stratified based on t½, the antibody titers against circumsporozoite protein and merozoite surface protein 1 were significantly higher in participants who cleared parasites rapidly in the AL group (P = .01 and P = .02, respectively). CONCLUSION: Data presented here define immunoprofiles associated with distinct responses to 2 different antimalarial drugs, revealing impact of preexisting immunity on the efficacy of artemisinin combination therapy regimens in a malaria-holoendemic area. CLINICAL TRIALS REGISTRATION: NCT01976780.

A seven-year surveillance of epidemiology of malaria reveals travel and gender are the key drivers of dispersion of drug resistant genotypes in Kenya.

Malaria drug resistance is a global public health concern. Though parasite mutations have been associated with resistance, other factors could influence the resistance. A robust surveillance system is required to monitor and help contain the resistance. This study established the role of travel and gender in dispersion of chloroquine resistant genotypes in malaria epidemic zones in Kenya. A total of 1,776 individuals presenting with uncomplicated malaria at hospitals selected from four malaria transmission zones in Kenya between 2008 and 2014 were enrolled in a prospective surveillance study assessing the epidemiology of malaria drug resistance patterns. Demographic and clinical information per individual was obtained using a structured questionnaire. Further, 2 mL of blood was collected for malaria diagnosis, parasitemia quantification and molecular analysis. DNA extracted from dried blood spots collected from each of the individuals was genotyped for polymorphisms in Plasmodium falciparum chloroquine transporter gene (Pfcrt 76), Plasmodium falciparum multidrug resistant gene 1 (Pfmdr1 86 and Pfmdr1 184) regions that are putative drug resistance genes using both conventional polymerase chain reaction (PCR) and real-time PCR. The molecular and demographic data was analyzed using Stata version 13 (College Station, TX: StataCorp LP) while mapping of cases at the selected geographic zones was done in QGIS version 2.18. Chloroquine resistant (CQR) genotypes across gender revealed an association with chloroquine resistance by both univariate model (p = 0.027) and by multivariate model (p = 0.025), female as reference group in both models. Prior treatment with antimalarial drugs within the last 6 weeks before enrollment was associated with carriage of CQR genotype by multivariate model (p = 0.034). Further, a significant relationship was observed between travel and CQR carriage both by univariate model (p = 0.001) and multivariate model (p = 0.002). These findings suggest that gender and travel are significantly associated with chloroquine resistance. From a gender perspective, males are more likely to harbor resistant strains than females hence involved in strain dispersion. On the other hand, travel underscores the role of transport network in introducing spread of resistant genotypes, bringing in to focus the need to monitor gene flow and establish strategies to minimize the introduction of resistance strains by controlling malaria among frequent transporters.

Serological Evidence of Yersiniosis, Tick-Borne Encephalitis, West Nile, Hepatitis E, Crimean-Congo Hemorrhagic Fever, Lyme Borreliosis, and Brucellosis in Febrile Patients Presenting at Diverse Hospitals in Kenya.

Data on pathogen prevalence is crucial for informing exposure and disease risk. We evaluated serological evidence of tick-borne encephalitis (TBE), West Nile (WN), Hepatitis E virus (HEV), Crimean-Congo Hemorrhagic Fever (CCHF), Yersiniosis, Lyme Disease (LD), and brucellosis in 1033 patients presenting with acute febrile illness at 9 health care facilities from diverse ecological zones of Kenya: arid and semiarid (Garissa District Hospital, Lodwar District Hospital, Marigat District Hospital, Gilgil District Hospital), Lake Victoria basin (Kisumu District Hospital, Alupe District Hospital, Kombewa Sub-County Hospital), Kisii highland (Kisii District Hospital), and coastal (Malindi District Hospital). Epidemiological information of the patients such as geography, age, gender, and keeping animals were analyzed as potential risk factors. Of the 1033 samples, 619 (59.9%) were seropositive to at least one pathogen by IgM (current exposure), IgG/IgM (recent exposure), and IgG (past exposure). Collective seroprevalence for current, recent, and past to the pathogens was 9.4%, 5.1%, and 21.1% for LD; 3.6%, 0.5%, and 12.4% for WN; 0.9%, 0.5%, and 16.9% for HEV; 5.8%, 1.3%, and 3.9% for brucellosis; 5.7%, 0.2%, and 2.3% for yersiniosis; 1.7%, 0%, and 6.2% for TBE; and 0.4%, 0%, and 1.9% for CCHF. Brucellosis risk was higher in patients recruited at Garissa District Hospital (odds ratio [OR] = 3.41), HEV (OR = 2.45) and CCHF (OR = 5.46) in Lodwar District Hospital, LD in Alupe District Hospital (OR = 5.73), Kombewa Sub-district hospital (OR = 8.17), and Malindi District hospital (OR = 3.3). Exposure to LD was highest in the younger age group, whereas yersiniosis did not vary with age. Age was a significant risk for WN, brucellosis, CCHF, TBE, and HEV and in those aged >14 years there was an increased risk to WN (OR = 2.30, p < 0.0001), brucellosis (OR = 1.84, p = 0.005), CCHF (OR = 4.35, p = 0.001), TBE (OR = 2.78, p < 0.0001), and HEV (OR = 1.94, p = 0.0001). We conclude that LD is pervasive and constitutes a significant health burden to the study population, whereas yersiniosis and CCHF are not significant threats. Going forward, community-based studies will be needed to capture the true seroprevalence rates and the associated risk factors.