Makepeace BL et al. (2015) Expert Rev Vaccines "The case for vaccine development in the strategy to eradicate river blindness (onchocerciasis) from Africa."

Makepeace BL, Lustigman S, Babayan SA, Taylor DW

[Expert Rev Vaccines, 2015]

Onchocerciasis or river blindness is a neglected parasitic disease causing severe dermatitis and visual impairment, predominantly in Africa. Historically, onchocerciasis control targeted vector breeding sites, but the current strategy relies on mass administration of a single drug, ivermectin. As programmatic goals shift from reducing public health impact to active elimination, sole reliance on ivermectin is threatened by contraindications in areas coendemic for loiasis, an inability to break transmission in some foci, and the emergence of drug resistance. Here, we argue that prophylactic and therapeutic vaccines would accelerate elimination efforts and safeguard the enormous strides made in onchocerciasis control. These vaccines could be based on one or more of three lead candidates identified by a newly formed transatlantic partnership, The Onchocerciasis Vaccine for Africa Initiative.

Derry WB (2023) FEBS J "Role of developmental pathways in disease."

Derry WB

[FEBS J, 2023]

Developmental programs are tightly regulated networks of molecular and cellular signaling pathways that orchestrate the formation and organization of tissues and organs during organismal development. However, these programs can be disrupted or activated in an untimely manner, or in the wrong tissues, and this can lead to a host of diseases. This aberrant re-activation can occur due to a multitude of factors, including genetic mutations, environmental influences, or epigenetic modifications. Consequently, cells may undergo abnormal growth, differentiation, or migration, leading to structural abnormalities or functional impairments at the tissue or organismal level. This Subject Collection of The FEBS Journal on Developmental Pathways in Disease highlights 11 reviews and three research articles that cover a broad array of topics focused on the role of signaling pathways critical for normal development that are deregulated in human disease.

Garrity PA (2007) J Neurophysiol "Role of adaptation in C. elegans thermotaxis. Focus on "Short-term adaptation and temporal processing in the cryophilic response of Caenorabditis elegans"."

Garrity PA

[J Neurophysiol, 2007]

The work of Clark et al. in this issue of J. Neurophysiology extends the analysis of thermotaxis in C. elegans by providing a detailed analysis of the adaptation of thermotactic behavior. Previous work indicates that thermotaxis in C. elegans involves a biased random walk in which changes in temperature alter the duration of the runs that an animal makes between turns. Interestingly, the authors find that although behavioral responses to increases and decreases in temperature have opposite effects on run length, the two responses are of similar magnitude and adapt with similar kinetics. These properties are predicted to allow the system act as a band-pass filter that would be less sensitive to temperature fluctuations occurring on a time-scale significantly faster or slower than the time needed for an average run. This analysis of C. elegans thermotaxis raises potential parallels to bacterial chemotaxis, with the kinetics of adaptation playing an important role in determining the ability of the organism to sense a stimulus gradient. This raises the possibility that diverse organisms may exploit similar system properties to solve similar problems, such as the problem of responding robustly to subtle gradations in an external stimulus.

Corsi AK et al. (2015) Genetics "A Transparent Window into Biology: A Primer on Caenorhabditis elegans."

Corsi AK, Chalfie M, Wightman B

[Genetics, 2015]

A little over 50 years ago, Sydney Brenner had the foresight to develop the nematode (round worm) Caenorhabditis elegans as a genetic model for understanding questions of developmental biology and neurobiology. Over time, research on C. elegans has expanded to explore a wealth of diverse areas in modern biology including studies of the basic functions and interactions of eukaryotic cells, host-parasite interactions, and evolution. C. elegans has also become an important organism in which to study processes that go awry in human diseases. This primer introduces the organism and the many features that make it an outstanding experimental system, including its small size, rapid life cycle, transparency, and well-annotated genome. We survey the basic anatomical features, common technical approaches, and important discoveries in C. elegans research. Key to studying C. elegans has been the ability to address biological problems genetically, using both forward and reverse genetics, both at the level of the entire organism and at the level of the single, identified cell. These possibilities make C. elegans useful not only in research laboratories, but also in the classroom where it can be used to excite students who actually can see what is happening inside live cells and tissues.

Kazura JW (2016) Am J Trop Med Hyg "Onchocerciasis Elimination from Africa: One Step in Northern Sudan."

Kazura JW

[Am J Trop Med Hyg, 2016]

Onchocerciasis is one of the two filarial helminth "neglected tropical diseases" (the other being lymphatic filariasis) that has been targeted for geographically local elimination followed by global eradication. The last known areas of Onchocerca volvulus transmission in the Americas have recently been reported to be eliminated. In contrast, achieving metrics for interruption of O. volvulus transmission in Africa, thus removing the requirement for continued monitoring and mass drug administration (MDA) with ivermectin, has been more challenging. To date, transmission cessation of O. volvulus has been validated only in the Mount Elgon region of eastern Uganda. Annual and biannual ivermectin MDA was delivered in this endemic focus from 1994 to 2011, in combination with sustained vector control aimed at reducing the local larval Simulium neavei vectors that have a phoretic association with freshwater crabs. Subsequent to this accomplishment, the World Health Organization (WHO) updated in 2016 the criteria for stopping MDA as a result of transmission interruption. The technical procedures and the corresponding cutoff values to signify transmission interruption included the following: 1) screening pools of black flies by polymerase chain reaction for the DNA repeat sequence Ov150; minimal elimination value is < 1/2,000 Ov150-positive flies and 2) serologic screening of school-aged children < 10 years of age for immunoglobulin G4 antibodies to the Ov16 antigen; elimination value is antibody prevalence < 0.1%. In this issue of the American Journal of Tropical Medicine and Hygiene, Zarroug and others describe results of a 3-year post-MDA treatment survey that confirm elimination of O. volvulus transmission by these criteria in Abu Hamed, a geographically isolated endemic focus in northern Sudan inhabited by approximately 120,000 people. Of the 5,266 children tested for Ov16 antibody, one 9-year-old child was positive. This child had never traveled outside her home village and had a negative skin snip for Ov150 DNA, indicating that she probably did not have a patent infection with skin microfilariae, but had previously been exposed to O. volvulus infective larvae. Lymphatic filariasis or other parasitic worm infections that may elicit antibodies that cross-react with Ov16 are not endemic in the study area.