Insensitivity to pain is a rare disorder that is commonly associated with Hereditary and Sensory Autonomic Neuropathies (HSAN I -V) resulting often in autonomic dysfunction and premature death. Very few individuals have been reported with pain insensitivity lacking such autonomic neuropathies. We performed genetic, neurologic, psychological, and psychophysical evaluations in such an individual (OMIM 243000) and her first degree relatives. Sequence analysis of genomic DNA revealed two novel SCN9A mutations in this index case (IC). One was a non-conservative missense mutation (C1719R) in exon 26 present only in the IC and one parent. Further sequence analysis of the child's DNA revealed a 1-bp splice donor deletion in intron 17 which was also present in the other parent and one sibling. Detailed psychophysical testing was used to phenotypically characterize the IC, her family members, and 10 matched normal controls. Similar to family members and controls the IC showed normal somatosensory functioning for nonnociceptive mechanoreception and warmth. However, she demonstrated diminished ability to detect cool temperatures combined with profound deficits in heat and mechanical nociception. Congenital insensitivity to pain in our IC was associated with two novel SCN9A mutations which most likely resulted in a Nav1.7 channelopathy. However, in contrast to individuals with other SCN9A mutations, the observed pain insensitivity was relative and not absolute, which may be consistent with hypomorphic effects of one or both mutations. The ability to sense at least some danger signals may be advantageous and ameliorate the otherwise increased morbidity and mortality of some individuals with congenital insensitivity to pain.

Abstract. Administering primaquine (PQ) to treat malaria patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency can pose a serious risk of drug-induced hemolysis (DIH). New easy to use point-of-care rapid diagnostic tests are being developed as an alternative to labor-intensive spectrophotometric methods, but they require field testing before they can be used at scale. This study screened 456 participants in Gressier, Haiti using the Access Bio CareStart qualitative G6PD rapid detection test compared with the laboratory-based Trinity Biotech quantitative spectrophotometric assay. Findings suggest that the CareStart test was 90% sensitive for detecting individuals with severe deficiency and 84.8% sensitive for detecting individuals with moderate and severe deficiency compared with the Trinity Biotech assay. A high negative predictive value of 98.2% indicates excellent performance in determining those patients able to take PQ safely. The CareStart G6PD test holds much value for screening malaria patients to determine eligibility for PQ therapy.

BackgroundMalaria transmission continues to occur in Haiti, with 25,423 confirmed cases of Plasmodium falciparum and 161,236 suspected infections reported in 2012. At low prevalence levels, passive surveillance measures, which rely primarily on reports from health systems, becomes less appropriate for capturing annual malaria incidence. To improve understanding of malaria transmission in Haiti, participants from the Ouest and Sud-Est departments were screened using a highly sensitive enzyme-linked immunosorbent assay (ELISA).MethodsBetween February and May 2013, samples were collected from four different sites including a rural community, two schools, and a clinic located in the Ouest and Sud-Est departments of Haiti. A total of 815 serum samples were screened for malaria antibodies using an indirect ELISA coated with vaccine candidates apical membrane antigen (AMA-1) and merozoite surface protein-1 (MSP-119). The classification of previous exposure was established by using a threshold value that fell three standard deviations above the mean absorbance for suspected seronegative population members (OD of 0.32 and 0.26 for AMA-1 and MSP-1, respectively). The observed seroprevalence values were used to fit a modified reverse catalytic model to yield estimates of seroconversion rates.ResultsOf the samples screened, 172 of 815 (21.1%) were AMA-1 positive, 179 of 759 (23.6%) were MSP-119 positive, and 247 of 815 (30.3%) were positive for either AMA-1 or MSP-1; indicating rates of previous infections between 21.1% and 30.3%. Not surprisingly, age was highly associated with the likelihood of previous infection (p-value <0.001). After stratification by age, the estimated seroconversion rate indicated that the annual malaria transmission in the Ouest and Sud-Est department is approximately 2.5% (95% CI SCR: 2.2%, 2.8%).ConclusionsThese findings suggest that despite the absence of sustained malaria control efforts in Haiti, transmission has remained relatively low over multiple decades. Elimination in Haiti appears to be feasible; however, surveillance must continue to be strengthened in order to respond to areas with high transmission and measure the impact of future interventions.

No abstract