Normal Clinical Laboratory Ranges by Age and Sex, and Impact on Study Screening Outcomes in Rural Mali.

The interpretation of a laboratory test result requires an appropriate reference range established in healthy subjects, and normal ranges may vary by factors such as geographic region, sex, and age. We examined hematological and clinical chemistry parameters in healthy residents at two rural vaccine trial sites: Bancoumana and Doneguebougou in Mali, West Africa. During screening of clinical studies in 2018 and 2019, peripheral blood samples from 1,192 apparently healthy individuals age 6 months to 82 years were analyzed at a laboratory accredited by the College of American Pathologists for a complete blood count, and creatinine and/or alanine aminotransferase levels. Based on manufacturers' reference range values, which are currently used in Malian clinical laboratories, abnormal values were common in this healthy population. In fact, 30.4% of adult participants had abnormal neutrophil levels and 19.8% had abnormal hemoglobin levels. Differences by sex were observed in those who were older, but not in those younger than 10 years, for several parameters, including hemoglobin, platelet, and absolute neutrophil counts in hematology, and creatinine in biochemistry. The site-specific reference intervals we report can be used in malaria vaccine clinical trials and other interventional studies, as well as in routine clinical care, to identify abnormalities in hematological and biochemical parameters among healthy Malian trial participants.

Susceptibility of Anopheles gambiae and Anopheles stephensi to tropical isolates of Plasmodium falciparum.

BACKGROUND: The susceptibility of anopheline mosquito species to Plasmodium infection is known to be variable with some mosquitoes more permissive to infection than others. Little work, however, has been carried out investigating the susceptibility of major malaria vectors to geographically diverse tropical isolates of Plasmodium falciparum aside from examining the possibility of infection extending its range from tropical regions into more temperate zones. METHODS: This study investigates the susceptibility of two major tropical mosquito hosts (Anopheles gambiae and Anopheles stephensi) to P. falciparum isolates of different tropical geographical origins. Cultured parasite isolates were fed via membrane feeders simultaneously to both mosquito species and the resulting mosquito infections were compared. RESULTS: Infection prevalence was variable with African parasites equally successful in both mosquito species, Thai parasites significantly more successful in An. stephensi, and PNG parasites largely unsuccessful in both species. CONCLUSION: Infection success of P. falciparum was variable according to geographical origin of both the parasite and the mosquito. Data presented raise the possibility that local adaptation of tropical parasites and mosquitoes has a role to play in limiting gene flow between allopatric parasite populations.

Haptoglobin levels are associated with haptoglobin genotype and alpha+ -Thalassemia in a malaria-endemic area.

Haptoglobin (Hp) is an acute phase protein that removes free hemoglobin (Hb) released during hemolysis. Hp has also been shown to be toxic for malaria parasites. alpha(+)-Thalassemia is a hemoglobinopathy that results in subclinical hemolytic anemia. alpha(+)-Thassemia homozygosity confers protection against severe malarial disease by an as yet unidentified mechanism. Hp levels were measured in a serial cross-sectional survey of children in Madang Province, Papua New Guinea (PNG). Hp levels were related to age, Hp genotype, Hb levels, parasitemia, splenomegaly, and alpha(+)-thalassemia genotype. Surprisingly, children who were homozygous for alpha(+) -thalassemia had significantly higher levels of Hp than did heterozygotes, after controlling for relevant confounders. We suggest that this is the result of either reduced mean cell Hb associated with alpha(+) -thalassemia homozygosity or an elevated IL-6-dependent acute phase response.

Human migration, mosquitoes and the evolution of Plasmodium falciparum.

To date, coalescent analysis of the Plasmodium falciparum genome sequence has failed to provide a unifying theory regarding the parasite's evolution. While a better understanding of the evolution of the malaria genome will undoubtedly clarify the current controversy, the importance of the parasite's interplay with both the human host and mosquito vector cannot be underestimated. Changes in the population biology or ecology of either one of these species have consequences for malaria transmission and this was never more apparent than in the environmental changes brought about by the advent of agriculture.