Date of Award

January 2021

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Sunil Parikh

Abstract

Five Plasmodium species (P. falciparum, P. vivax, P. malaria, P. ovale, and P. knowlesi) result in human malaria infection. Malaria diagnosis has traditionally relied on microscopy, and more recently, on rapid diagnostic tests (RDT), but these diagnostic modalities have high rates of false negatives for low-parasitemia, non-P. falciparum infection such as P. malariae. Molecular-based diagnostics have emerged as the gold standard for malaria diagnosis. Cameroon endures a high malaria burden, and all four main Plasmodium species have been detected within the country. Febrile, symptomatic patients presenting to the Emergency Department of the Douala Military Hospital were enrolled and assessed for symptoms. A venous blood sample was used to perform a pan-Plasmodium RDT, test hemoglobin level, prepare thick and thin blood smears for microscopy, and prepare dried blood spots (DBS) for molecular-based analyses. Cultured parasites were also used to generate DBS with known parasitemia. Speciation was performed using nested PCR assays. Anemia was defined according to WHO criteria. Between July and November 2018, 555 participations were enrolled, and the sample included 50% women, individuals from all districts across Douala, and persons aged 3 months to 86 years. Fatigue, headache, and myalgias/arthralgias were common presenting symptoms, and anemia was present in 39% of participants. Anemia was higher among children and women compared to adult men, and koilonychia and moderate-severe pallor had high positive likelihood ratios for anemia. RDT detected Plasmodium spp. in 24.8% of participants, while 34.6% of participants were positive for malaria by PCR. There were 181 P. falciparum mono-infections (33.5%), 4 P. malaria/P. falciparum mixed infections (0.7%), and 2 P. falciparum/P. ovale mixed infections (0.4%). The limit of detection of the PCR speciation assay was determined to be 10-4% parasitemia. Travel to the northern regions, high fever at presentation, and emesis multiple times a day were associated with high likelihood ratios for malaria infection. Malaria was found to be a predictor of anemia, and children with malaria were more likely to have anemia compared to children without malaria (odds ratio: 5.42, 95% CI: 2.33–12.59). The four P. falciparum/P. malariae mixed infections occurred in younger patients from across Douala, and the RDT correctly identified mixed infection in only two of the four cases. This study revealed a high incidence of malaria, with peak malaria burden shifted to older children, and a high prevalence of anemia. P. malariae was shown to be actively circulating in Douala, although the prevalence was far lower than hypothesized. By assessing demographic and clinical variables, the study showed how health centers, such as the Douala Military Hospital, can generate pre-test probabilities for diagnoses such as anemia and malaria and define likelihood ratios for clinical findings specifically for their population. These results will inform health care delivery and malaria control efforts at the Doula Military Hospital, within Douala, and across Cameroon.

Comments

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